Association of polygenic score and the involvement of cholinergic and glutamatergic pathways with lithium treatment response in patients with bipolar disorder.

Lithium is regarded as the first-line treatment for bipolar disorder (BD), a severe and disabling mental health disorder that affects about 1% of the population worldwide. Nevertheless, lithium is not consistently effective, with only 30% of patients showing a favorable response to treatment. To provide personalized treatment options for bipolar patients, it is essential to identify prediction biomarkers such as polygenic scores. In this study, we developed a polygenic score for lithium treatment response (Li+PGS) in patients with BD. To gain further insights into lithium's possible molecular mechanism of action, we performed a genome-wide gene-based analysis. Using polygenic score modeling, via methods incorporating Bayesian regression and continuous shrinkage priors, Li+PGS was developed in the International Consortium of Lithium Genetics cohort (ConLi+Gen: N = 2367) and replicated in the combined PsyCourse (N = 89) and BipoLife (N = 102) studies. The associations of Li+PGS and lithium treatment response - defined in a continuous ALDA scale and a categorical outcome (good response vs. poor response) were tested using regression models, each adjusted for the covariates: age, sex, and the first four genetic principal components. Statistical significance was determined at P < 0.05. Li+PGS was positively associated with lithium treatment response in the ConLi+Gen cohort, in both the categorical (P = 9.8 × 10-12, R2 = 1.9%) and continuous (P = 6.4 × 10-9, R2 = 2.6%) outcomes. Compared to bipolar patients in the 1st decile of the risk distribution, individuals in the 10th decile had 3.47-fold (95%CI: 2.22-5.47) higher odds of responding favorably to lithium. The results were replicated in the independent cohorts for the categorical treatment outcome (P = 3.9 × 10-4, R2 = 0.9%), but not for the continuous outcome (P = 0.13). Gene-based analyses revealed 36 candidate genes that are enriched in biological pathways controlled by glutamate and acetylcholine. Li+PGS may be useful in the development of pharmacogenomic testing strategies by enabling a classification of bipolar patients according to their response to treatment.

Investigating the phenotypic and genetic associations between personality traits and suicidal behavior across major mental health diagnoses.

Personality traits influence risk for suicidal behavior. We examined phenotype- and genotype-level associations between the Big Five personality traits and suicidal ideation and attempt in major depressive, bipolar and schizoaffective disorder, and schizophrenia patients (N = 3012) using fixed- and random-effects inverse variance-weighted meta-analyses. Suicidal ideations were more likely to be reported by patients with higher neuroticism and lower extraversion phenotypic scores, but showed no significant association with polygenic load for these personality traits. Our findings provide new insights into the association between personality and suicidal behavior across mental illnesses and suggest that the genetic component of personality traits is unlikely to have strong causal effects on suicidal behavior.

Quality of life and subjective sleep-related measures in bipolar disorder and major depressive disorder.

PURPOSE: Diminished quality of life (QoL) has been reported in patients with mood disorders. QoL has also been shown to be decreased by sleep disturbances. Since sleep disorders are common in mood disorders, the aim of this study was to determine whether sleep characteristics are associated to QoL among patients with Bipolar Disorder (BD) and unipolar Major Depressive Disorders (MDD). METHODS: QoL was assessed in 170 patients with mood disorders (61 BD and 109 MDD), who also completed questionnaires measuring the severity of insomnia, sleepiness, chronotype preference and obstructive sleep apnea (OSA) probability index. RESULTS: Analyses showed that BD and MDD groups had similar QoL and sleep measures but the MDD group had higher OSA scores. In BD, correlations indicated a relationship between QoL and insomnia complaints and sleepiness, whereas in MDD, correlations indicated an association between QoL and insomnia complaints and OSA score. In both groups, QoL was related to depressive symptomatology. Linear regressions showed that, in BD, QoL was related to insomnia complaints and sleepiness even in the euthymic state, whereas in MDD, QoL was related to insomnia complaints but not in euthymic patients. CONCLUSION: QoL is related to sleep differently in BD and MDD. The results suggest that insomnia and sleepiness are particularly high in BD even when patients are euthymic. These findings suggest that focusing on insomnia and sleepiness during different mood states of BD could increase QoL.

Insomnia disorders are associated with increased cardiometabolic disturbances and death risks from cardiovascular diseases in psychiatric patients treated with weight-gain-inducing psychotropic drugs: results from a Swiss cohort.

STUDY OBJECTIVES: Insomnia disorders as well as cardiometabolic disorders are highly prevalent in the psychiatric population compared to the general population. We aimed to investigate their association and evolution over time in a Swiss psychiatric cohort. METHODS: Data for 2861 patients (8954 observations) were obtained from two prospective cohorts (PsyMetab and PsyClin) with metabolic parameters monitored routinely during psychotropic treatment. Insomnia disorders were based on the presence of ICD-10 "F51.0" diagnosis (non-organic insomnia), the prescription of sedatives before bedtime or the discharge letter. Metabolic syndrome was defined using the International Diabetes Federation definition, while the 10-year risk of cardiovascular event or death was assessed using the Framingham Risk Score and the Systematic Coronary Risk Estimation, respectively. RESULTS: Insomnia disorders were observed in 30% of the cohort, who were older, predominantly female, used more psychotropic drugs carrying risk of high weight gain (olanzapine, clozapine, valproate) and were more prone to suffer from schizoaffective or bipolar disorders. Multivariate analyses showed that patients with high body mass index (OR = 2.02, 95%CI [1.51-2.72] for each ten-kg/m2 increase), central obesity (OR = 2.20, [1.63-2.96]), hypertension (OR = 1.86, [1.23-2.81]), hyperglycemia (OR = 3.70, [2.16-6.33]), high density lipoprotein hypocholesterolemia in women (OR = 1.51, [1.17-1.95]), metabolic syndrome (OR = 1.84, [1.16-2.92]) and higher 10-year risk of death from cardiovascular diseases (OR = 1.34, [1.17-1.53]) were more likely to have insomnia disorders. Time and insomnia disorders were associated with a deterioration of cardiometabolic parameters. CONCLUSIONS: Insomnia disorders are significantly associated with metabolic worsening and risk of death from cardiovascular diseases in psychiatric patients.

Is Coping with Stigma by Association Role-Specific for Different Family Members? A Qualitative Study with Bipolar Disorder Patients' Relatives.

Trying to cope with stigma by association (SBA) often results in behaviors leading to social isolation and withdrawal. This study aimed at exploring the stigma-related experiences of family members of persons living with bipolar disorder (PW-BD). A semi-structured interview was conducted with relatives of PW-BD. Open-ended questions addressed three issues: awareness of public stigma of bipolar disorder, experiences of associative stigma, and ways of coping with experiences of SBA. Data were collected from a purposive sample of 21 family members. Experiences of SBA were specifically related to the different family roles. Parents had to deal with responsibility, partners with the choice of staying or not, and siblings with "a sort of duty." These specific prejudices enhanced specific coping strategies. This is the first study to highlight specific issues and coping from the perspective of family members. Based on these findings, specific targeted interventions could be developed.

[Stigma and self-stigma in psychiatric diseases: current issues and practices]. / Stigmatisation et autostigmatisation dans les maladies psychiatriques: enjeux et pratiques actuels.

Stigmatization and self-stigmatization of people suffering from mental disorders have been denounced for several years, however they still impact treatment and identity construction. Education, social sharing, and institutional engagement are interventions that challenge public stigma. Interventions based on individual or group therapies that oppose self-stigma proved effective. Questions regarding the effects of media coverage or the intersectionality of stigmatized identities remain open. In this article, we made a summary of the current situation based on recent literature.

Bien que dénoncées depuis plusieurs années, la stigmatisation et l'autostigmatisation des personnes souffrant de troubles psychiques ont un impact toujours très négatif, tant en termes de soins que de construction identitaire. Différents types d'interventions ont été élaborés pour lutter contre la stigmatisation publique, tels les interventions éducationnelles, le partage du vécu ou l'engagement institutionnel. Quant à la prise en charge de l'autostigmatisation, elle repose sur des thérapies individuelles ou groupales dont l'efficacité est de mieux en mieux étayée. Néanmoins, d'autres questionnements persistent comme les effets de la médiatisation ou l'intersectionnalité des identités stigmatisées. Dans cet article, nous proposons un bref résumé de la situation actuelle à partir de la littérature récente.

Effect of Ketamine on Rumination in Treatment-Resistant Depressive Patients.

BACKGROUND: A rapid antidepressant effect of ketamine has repeatedly been documented in the literature, and identifying clinical features associated with a better response to this treatment is currently an essential question. Considering the relationship between rumination and depression and the need to identify potential predictors of response to ketamine, we analyzed the effect of a single injection of ketamine 0.5 mg/kg on rumination in treatment-resistant depressive (TRD) patients and explored whether baseline ruminative style and early improvements of rumination would predict a greater antidepressant effect of ketamine. METHODS: Ten TRD outpatients who participated in a 4-week open study on the antidepressant effect of ketamine also completed the Ruminative Response Scale the day before, the day after, and a week after ketamine administration. RESULTS: We found that in our patients, a single rapid 1-minute intravenous injection of ketamine 0.5 mg/kg was efficacious in reducing rumination, but neither severity of rumination at baseline nor early improvements of rumination after ketamine injection predicted antidepressant response. CONCLUSIONS: Our preliminary data suggest that a single injection of ketamine 0.5 mg/kg can be efficacious in reducing rumination in TRD patients but rumination does not seem to be a useful clinical predictor of response to ketamine. Larger studies are necessary to confirm these results.

Training junior faculty to become clinical teachers: The value of personalized coaching.

Background: Junior clinical faculty require institutional support in the acquisition of feedback and clinical supervision skills of trainees. We tested the effectiveness of a personalized coaching versus guided self-reflection format of a faculty development program at improving faculty skills and self-efficacy.Methods: Participants were evaluated both before and after the program using a four-station Objective Structured Teaching Exercise (OSTE). A gain-score analysis, one-way ANOVA, and paired t-tests were used to evaluate both groups. The impact on the learning environment was measured by resident ratings of the Maastricht Clinical Teaching Questionnaire.Results: One hundred and twenty-seven participants completed the study over a three-year period. Both groups had significant improvements in self-efficacy. Participants in the coaching group demonstrated superior performance in encouraging learner self-reflection, teaching effectiveness, verifying learner understanding, exploring feelings/needs, and defining learning objectives. Over a 5-year period, the overall institutional learning climate significantly improved concerning faculty role-modeling, coaching, articulation, and explorations skills.Conclusion: Offering a contextualized faculty-development program using OSTEs that provides multiple opportunities for feedback and is focused on creating a community of practice is an effective method to facilitate the transfer of skills to the clinical environment, supports teacher identity development, and favorably impacts the learning climate.

Self-Destigmatization Process? Experiences of Persons Living with Bipolar Disorder: A Qualitative Study.

This qualitative study investigated subjective experiences of self-stigmatization and self-destigmatization among people living with bipolar disorder (BD). We conducted in-depth interviews focusing on self-stigmatization and self-destigmatization with 22 individuals living with BD. The interview transcripts were thematically analyzed using a mixed inductive and deductive approach. Thirty-six codes were extracted and organized into six themes: language, behaviors, relationships, personal experience, identity, and healthcare. Each theme was characterized by an evolution process, and the codes were distributed in a step-by-step order as landmarks. The process begins with the experience of self-stigmatization, and develops toward self-destigmatization. This study presents a new six-dimension process called the "self-destigmatization process" (SDP), a personal and interrelational process that deconstructs self-stigmatization. Clinicians can use the landmarks of the process for clinical assessment and therapeutic interventions to increase recovery orientation.

[Light - darkness and bipolar disorder]. / Lumière ­ obscurité et trouble bipolaire.

Circadian rhythmicity generated by the biological clock structures the functioning of human beings over a period of almost 24 hours. This clock is entrained daily by internal and external cues among which light is the most powerful. Several disturbances, whether clinical or biological, observed in bipolar disorders are suggestive of a disruption of the circadian rhythm. Thus, treatments that modulate the biological clock have been developed. So far, the results of light therapy are not unanimous and invite us to better specify the treatment modalities. Dark therapy is a promising intervention that is still not much studied nowadays and therefore opens up great prospects for research in the future.

Le rythme circadien généré par l'horloge biologique structure le fonctionnement de l'être humain sur une période de presque 24 heures. Cette horloge est quotidiennement «â€…mise à l'heure ¼ par des synchronisateurs internes et externes parmi lesquels la lumière est la plus puissante. Plusieurs perturbations tant cliniques que biologiques observées chez les personnes souffrant d'un trouble bipolaire sont évocatrices d'un dérèglement du rythme circadien. Ainsi, des traitements permettant de moduler l'horloge biologique ont été développés. Actuellement, les résultats de la luminothérapie ne sont pas unanimes et cela nous invite à mieux préciser les modalités du traitement. La thérapie par l'obscurité est une intervention prometteuse, peu étudiée et ouvre donc de belles perspectives de recherche.

Medical students' professional identity development from being actors in an objective structured teaching exercise.

INTRODUCTION: Medical students develop professional identity through structured activities and impromptu interactions in various settings. We explored if contributing to an Objective Structured Teaching Exercise (OSTE) influenced students' professional identity development. METHODS: University clinical faculty members participated in a faculty development program on clinical supervision. Medical students who participated in OSTEs as simulated residents were interviewed in focus groups about what they learnt from the experience and how the experience influenced their vision of learning and teaching. Transcripts were analyzed using the Goldie's personality and social structure perspective model. RESULTS: Twenty-five medical students out of 32 students involved in OSTEs participated. On an institutional level, students developed a feeling of belonging to the institution. At an interactional level, students realized they could influence the teaching interaction by actively seeking or giving feedback. On the personal level, students realized that errors could become sources of learning and felt better prepared to receive faculty feedback. CONCLUSION: Taking part in OSTEs as a simulated resident has a positive impact on students' vision regarding the institution as a learning environment and their own role by actively seeking or giving feedback. OSTEs support their professional identity development regarding learning and teaching while sustaining faculty development.

Physicians' Perceptions and Experiences Regarding Leadership: A Link Between Beliefs and Identity Formation.

Introduction: Despite the development of national recommendations and training programs for effective leadership, junior and senior medical leaders often find themselves ill-prepared to take on these new responsibilities. This study aimed to explore physicians' perceptions, feelings, and beliefs regarding leadership and to provide recommendations regarding appropriate training and institutional post-training support. Methods: We conducted a qualitative study at the Geneva University Hospitals. A purposeful sample of residents (R), fellows (F), attending physicians (A), and chairpersons (CP) were invited to participate in focus groups (or semi-structured interviews) between April and June 2021. We investigated their understanding of leadership, self-perception as leaders, difficulties, and paths to improvement in their leadership skills. Focus groups were transcribed verbatim and analyzed both inductively and deductively using Fishbein's model of behavior prediction and Irby's professional identity formation framework. Results: We conducted ten focus groups (R=3; F=4, A=2, and CP=1) and one interview (CP). Physicians expressed poor self-efficacy at all hierarchical levels: feelings of insecurity and confusion (R and F), frustration (A), and feeling stuck between divisional and institutional governance (CP). Such negative feelings were nurtured by personal beliefs with an intuitive and idealized representation of leadership. Beliefs focused more on personal characteristics rather than on skills, processes, or perceived institutional norms. Unclear expectations regarding physicians' role as leaders, overemphasis on academic achievement, and silo professional organizations fueled their feelings. Participants reported developing their leadership through trial and error, observing role models, and turning to personal resources rather than formal training. Conclusion: Our results show that physicians' leadership skills are still mainly acquired intuitively and that institutional norms do not encourage clarification of leadership roles and processes. Physician training in leadership skills, together with more explicit and clear institutional processes, may help to improve physicians' self-efficacy and develop their identity as leaders.

A Prospective Multicenter Longitudinal Analysis of Suicidal Ideation among Long-COVID-19 Patients.

Long coronavirus disease 19 (COVID-19) is an emerging multifaceted illness with the pathological hallmarks of chronic inflammation and neuropsychiatric symptoms. These pathologies have also been implicated in developing suicidal behaviors and suicidal ideation (SI). However, research addressing suicide risk in long COVID-19 is limited. In this prospective study, we aim to characterize SI development among long-COVID-19 patients and to determine the predictive power of inflammatory markers and long-COVID-19 symptoms-including those of psychiatric origin-for SI. During this prospective, longitudinal, multicenter study, healthy subjects and long-COVID-19 patients will be recruited from the University Hospital of Geneva, Switzerland, the University of Genova, the University of Rome "La Sapienza", and the University of San Francisco. Study participants will undergo a series of clinic visits over a follow-up period of 1 year for SI assessment. Baseline and SI-onset levels of inflammatory mediators in plasma samples, along with 12 long-COVID-19 features (post-exertional malaise, fatigue, brain fog, dizziness, gastrointestinal disturbance, palpitations, changes in sexual desire/capacity, loss/change of smell/taste, thirst, chronic cough, chest pain, and abnormal movements) will be collected for SI risk analysis. The proposed enrollment period is from 15 January 2024 to 15 January 2026 with targeted recruitment of 100 participants for each study group. The anticipated findings of this study are expected to provide important insights into suicide risk among long-COVID-19 patients and determine whether inflammation and psychiatric comorbidities are involved in the development of SI in these subjects. This could pave the way to more effective evidence-based suicide prevention approaches to address this emerging public health concern.

Self-stigma and bipolar disorder: A systematic review and best-evidence synthesis.

BACKGROUND: Bipolar disorder is a severe and chronic mental illness characterized by recurrent major depressive episodes and mania or hypomania. In addition to the burden of the disease and its consequences, self-stigma can impact people with bipolar disorder. This review investigates the current state of research in self-stigma in bipolar disorder. METHODS: An electronic search was carried out until February 2022. Three academic databases were systematically searched, and best-evidence synthesis was made. RESULTS: Sixty-six articles were related to self-stigma in bipolar disorder. Seven key themes were extracted from these studies: 1/ Comparison of self-stigma in bipolar disorder and other mental illnesses, 2/ Sociocultural context and self-stigma, 3/ Correlates and predictors of self-stigma, 4/ Consequences of self-stigma, 5/ Treatments and self-stigma, 6/ Management of self-stigma, and 7/ Self-stigma and recovery in bipolar disorder. LIMITATIONS: Firstly, a meta-analysis could not be performed due to the heterogeneity of the studies. Secondly, limiting the search to self-stigma has excluded other forms of stigma that also have an impact. Thirdly, the under-reporting of negative or nonsignificant results due to publication bias and unpublished studies might have limited the accuracy of this reviews' synthesis. CONCLUSION: Research on self-stigma in persons with bipolar disorder has been the focused on different aspects, and interventions to reduce self-stigmatization have been developed, but evidence of their effectiveness is still sparse. Clinicians need to be attentive to self-stigma, its assessment, and its empowerment in their daily clinical practice. Future work is required to establish valid strategies to fight self-stigma.

Perceived public stigma and perceived public exposure by persons living with bipolar disorder: A qualitative study.

BACKGROUND: Stigma impact the lives of persons living with bipolar disorder. AIM: The aim of this study was to explore how perceived public stigma is described by people living with bipolar disorder and examine the links between perceived public stigma and perceived public exposure. METHOD: Face-to-face in-depth interviews were conducted in a purposive sample of euthymic people living with bipolar disorder recruited in a mood disorder ambulatory unit. RESULTS: Thematic analysis of the transcript yielded five independent themes that were related to perceived public stigma. Perceived public stigma of bipolar disorder was modeled as comprising the three elements of public stigmas (stereotype, prejudice, and discrimination), with the addition of public exposure as a core component. CONCLUSION: The representation of bipolar disorder in society via newspapers, films/TV series, conferences, and celebrity self-disclosures is considered to have multiple impacts. People living with bipolar disorder have also reported a perceived public stigma of bipolar disorder that has both specific features and characteristics of general mental illness.

Current practices of psychoeducation interventions with persons with bipolar disorders: a literature review.

This review sought to summarize the literature on current practices and forms of psychoeducation in the management of patients with bipolar disorder (BD), including only randomized controlled trials to ensure the best level of evidence. An extensive review of the available literature was conducted using PubMed/MEDLINE, Embase, and PsychInfo databases from inception to April 28th, 2022. The search yielded 381 studies. Seventy articles were included after removing duplicates and applying the inclusion/exclusion criteria. A best-evidence synthesis was used to identify the key results of each study and summarize the outcomes. Eleven descriptive categories were made. They encompass different forms of psychoeducation compared or combined with other psychosocial interventions, varying in setting (individual or group), with or without family members, structured or unstructured, mediated or not by digital tools (smartphone, internet). Globally, these studies show that psychoeducation is important in the treatment of BD, as it leads to a decrease in relapses, mood episodes, hospitalizations, and improved functioning or quality of life. Some studies also showed the benefits of psychoeducation on the patient's level of knowledge of pharmacological treatment and the disorder or compliance with medication, as well as reduced self-stigma. The limitations of this review are linked to the selection of only RCTs and the reliance on their post-hoc analyses. This review confirms the benefit of psychoeducation and psychosocial interventions on the evolution of BD (in different outcomes, including quality of life, relapse, and rehospitalization rates, for example). More recent interventions, such as mindfulness or online psychoeducation, represent an interesting option but more evidence is needed.

What Feedback Content Do Clinical Teachers Address During OSTEs?

Purpose: How to give feedback is widely taught and assessed during Faculty Development programs. As part of such programs, clinical teachers can attend objective structured teaching sessions (OSTEs), during which they are asked to give feedback to simulated residents on different tasks. Study aimed at: -analysing the feedback content provided during these OSTEs; -evaluating the impact of the training phase, medical discipline, or observed task; -assessing the alignment between feedback content addressed by clinical teachers and content identified as essential by experts. Methods: We conducted a multimethod study. Clinical teachers (N=89) from five departments were trained to give feedback to residents in a six-month training program. Before and after training, they completed three OSTE stations which focused on tasks involving communication, interprofessional, physical exam or procedural skills. We analysed feedback content descriptively. ANOVA test was applied to evaluate feedback contents' influencing factors (ie participants' training phase, medical discipline, type of task addressed). For each OSTE, we analysed the percentage of items identified as essential by 3 experts that were addressed by clinical teachers during the feedback. Results: We analysed 317 feedback sessions and coded 5388 occurrences. Feedback content distribution was: targeted content (73%), other clinical content (20%), learning strategies (4%), and self-management/other (3%). Feedback was often negative (73%). The training phase did not influence the content addressed while the topic of the observed task and clinical teachers' specialization slightly did. Alignment between content identified by experts and addressed by clinical teachers during OSTEs was low (3-38%). Conclusion: Clinical teachers give mostly negative and targeted feedback according to the task. The poor alignment in selecting key content to be addressed is striking and should be further explored since clinical teachers may address elements of competence more according to their personal preferences than to residents' needs and context priorities.