Associations of white blood cell and platelet counts with specific depressive symptom dimensions in patients with bipolar disorder: Analysis of data from the FACE-BD cohort.

Evidences suggest that inflammation is increased in a subgroup of patients with depression. Moreover, increased peripheral inflammatory markers (cells and proteins) are associated with some, but not all depressive symptoms. On the other hand, similar studies on bipolar disorders mainly focused on blood cytokines. Here, we analysed data from a large (N = 3440), well-characterized cohort of individuals with bipolar disorder using Kendall partial rank correlation, multivariate linear regression, and network analyses to determine whether peripheral blood cell counts are associated with depression severity, its symptoms, and dimensions. Based on the self-reported 16-Item Quick Inventory of Depressive Symptomatology questionnaire scores, we preselected symptom dimensions based on literature and data-driven principal component analysis. We found that the counts of all blood cell types were only marginally associated with depression severity. Conversely, white blood cell count was significantly associated with the sickness dimension and its four components (anhedonia, slowing down, fatigue, and appetite loss). Platelet count was associated with the insomnia/restlessness dimension and its components (initial, middle, late insomnia and restlessness). Principal component analyses corroborated these results. Platelet count was also associated with suicidal ideation. In analyses stratified by sex, the white blood cell count-sickness dimension association remained significant only in men, and the platelet count-insomnia/restlessness dimension association only in women. Without implying causation, these results suggest that peripheral blood cell counts might be associated with different depressive symptoms in individuals with bipolar disorder, and that white blood cells might be implicated in sickness symptoms and platelets in insomnia/agitation and suicidal ideation.

Use of Social Media Data to Diagnose and Monitor Psychotic Disorders: Systematic Review.

BACKGROUND: Schizophrenia is a disease associated with high burden, and improvement in care is necessary. Artificial intelligence (AI) has been used to diagnose several medical conditions as well as psychiatric disorders. However, this technology requires large amounts of data to be efficient. Social media data could be used to improve diagnostic capabilities. OBJECTIVE: The objective of our study is to analyze the current capabilities of AI to use social media data as a diagnostic tool for psychotic disorders. METHODS: A systematic review of the literature was conducted using several databases (PubMed, Embase, Cochrane, PsycInfo, and IEEE Xplore) using relevant keywords to search for articles published as of November 12, 2021. We used the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) criteria to identify, select, and critically assess the quality of the relevant studies while minimizing bias. We critically analyzed the methodology of the studies to detect any bias and presented the results. RESULTS: Among the 93 studies identified, 7 studies were included for analyses. The included studies presented encouraging results. Social media data could be used in several ways to care for patients with schizophrenia, including the monitoring of patients after the first episode of psychosis. We identified several limitations in the included studies, mainly lack of access to clinical diagnostic data, small sample size, and heterogeneity in study quality. We recommend using state-of-the-art natural language processing neural networks, called language models, to model social media activity. Combined with the synthetic minority oversampling technique, language models can tackle the imbalanced data set limitation, which is a necessary constraint to train unbiased classifiers. Furthermore, language models can be easily adapted to the classification task with a procedure called "fine-tuning." CONCLUSIONS: The use of social media data for the diagnosis of psychotic disorders is promising. However, most of the included studies had significant biases; we therefore could not draw conclusions about accuracy in clinical situations. Future studies need to use more accurate methodologies to obtain unbiased results.

Association between anhedonia and suicidal events in patients with mood disorders: A 3-year prospective study.

BACKGROUND: As almost all mental disorders are associated with increased suicidal-related behavior, anhedonia might be a trans-diagnostic dimension to target for suicide prevention. METHODS: For this 3-year-long prospective study, 2,839 outpatients with mood disorders were recruited. They were divided in: (a) two groups according to the occurrence or not of suicidal ideation during the follow-up, and (b) two groups according to the occurrence or not of suicide attempts during the follow-up. Anhedonia was assessed using a composite score (the French version of the 14-item Snaith-Hamilton Pleasure Scale and item 13 of the Quick Inventory of Depressive Symptomatology scale) at inclusion and at 6, 12, 24, and 36 months after inclusion. RESULTS: Patients with mood disorders and anhedonia at least at one follow-up visit had a 1.4-fold higher risk of suicidal ideation (adjusted odds ratio = 1.35; 95% confidence interval [1.07, 1.70]), even after adjustment for confounding factors of suicide risk (i.e., bipolar or unipolar disorder, sex, age, marital status, education level, antidepressant intake, personal history of suicide attempt, at least one childhood trauma, and mean of the maximum depression score during the follow-up). Conversely, association between anhedonia and suicide attempt did not remain significant after adjustment. CONCLUSIONS: The significant association between anhedonia and suicide ideation in patients with mood disorders stresses the need of targeting hedonia in mood disorders, and of research focusing on the position to pleasure in life through eudaimonia.

Machine Learning and Natural Language Processing in Mental Health: Systematic Review.

BACKGROUND: Machine learning systems are part of the field of artificial intelligence that automatically learn models from data to make better decisions. Natural language processing (NLP), by using corpora and learning approaches, provides good performance in statistical tasks, such as text classification or sentiment mining. OBJECTIVE: The primary aim of this systematic review was to summarize and characterize, in methodological and technical terms, studies that used machine learning and NLP techniques for mental health. The secondary aim was to consider the potential use of these methods in mental health clinical practice. METHODS: This systematic review follows the PRISMA (Preferred Reporting Items for Systematic Review and Meta-analysis) guidelines and is registered with PROSPERO (Prospective Register of Systematic Reviews; number CRD42019107376). The search was conducted using 4 medical databases (PubMed, Scopus, ScienceDirect, and PsycINFO) with the following keywords: machine learning, data mining, psychiatry, mental health, and mental disorder. The exclusion criteria were as follows: languages other than English, anonymization process, case studies, conference papers, and reviews. No limitations on publication dates were imposed. RESULTS: A total of 327 articles were identified, of which 269 (82.3%) were excluded and 58 (17.7%) were included in the review. The results were organized through a qualitative perspective. Although studies had heterogeneous topics and methods, some themes emerged. Population studies could be grouped into 3 categories: patients included in medical databases, patients who came to the emergency room, and social media users. The main objectives were to extract symptoms, classify severity of illness, compare therapy effectiveness, provide psychopathological clues, and challenge the current nosography. Medical records and social media were the 2 major data sources. With regard to the methods used, preprocessing used the standard methods of NLP and unique identifier extraction dedicated to medical texts. Efficient classifiers were preferred rather than transparent functioning classifiers. Python was the most frequently used platform. CONCLUSIONS: Machine learning and NLP models have been highly topical issues in medicine in recent years and may be considered a new paradigm in medical research. However, these processes tend to confirm clinical hypotheses rather than developing entirely new information, and only one major category of the population (ie, social media users) is an imprecise cohort. Moreover, some language-specific features can improve the performance of NLP methods, and their extension to other languages should be more closely investigated. However, machine learning and NLP techniques provide useful information from unexplored data (ie, patients' daily habits that are usually inaccessible to care providers). Before considering It as an additional tool of mental health care, ethical issues remain and should be discussed in a timely manner. Machine learning and NLP methods may offer multiple perspectives in mental health research but should also be considered as tools to support clinical practice.

[Preventing suicide in general practice]. / Prévenir le suicide en médecine générale.

With one of the highest rates in Europe, suicide is a major public health problem in France. General practitioners are the backbone of the health system. They play a major role in suicide prevention. Mental health accounts for a large proportion of primary care practitioners' patients, the majority of which are for depressive and anxiety disorders. However, patients prefer to go to their general practitioner when they first encounter psychological difficulties. They are more likely to consult a mental health professional based on the advice of their general practitioner, hence the importance of linking primary and more specialised care.

[Towards freedom to claim the right to die]. / Vers une liberté à revendiquer le droit à mourir.

current evolution of society makes it possible to debate the issue of the end of life for people suffering from pathologies in which the vital prognosis is not involved; this concerns psychiatric situations in particular. This debate, which bears the seeds of a real desire to die as a personal choice, is likely to profoundly modify the doctor-patient relationship in the particular field of psychiatry.

Childhood maltreatment and clinical severity of treatment-resistant depression in a French cohort of outpatients (FACE-DR): One-year follow-up.

BACKGROUND: Childhood maltreatment is associated with major depressive disorder (MDD). It not only increases the risk of lifetime MDD, but it also aggravates its course. Among depressed patients, 20-30% of them experience treatment-resistance depression (TRD). We aimed to assess the association between childhood maltreatment, severity of depression in a unipolar TRD sample, and patient outcomes after one-year of follow-up. METHODS: Patients were recruited for a prospective cohort from the French network of TRD expert centers. Depressive symptom severity was assessed with the Montgomery-Åsberg Depression Rating Scale (MADRS) and the Quick Inventory of Depressive Symptomatology self-report (QIDS-SR). Childhood maltreatment was evaluated with the Childhood Trauma Questionnaire (CTQ). RESULTS: In total, 256 patients filled in the CTQ at baseline between 2012 and 2019. At baseline, the MADRS score was associated with CTQ score (ß = .185; p = .004). QIDS was also associated with CTQ scores (ß = .27; p < .001). Regarding the different subtypes of childhood maltreatment, MADRS was associated with physical (ß = .21; p = .005) and sexual abuse (ß = .22; p = .002), while QIDS with physical abuse (ß = .304; p < .001) and physical neglect (ß = .254; p < .001). However, we did not find any significant association focusing on the other types of traumas. During a 1-year follow-up focusing on remission, CTQ scores (baseline) were less important in remittent patients [n = 38; CTQ score = 39.26 (9.68)] than in nonremittent ones [n = 92; CTQ score = 46.02 (17.53)] (p = .027). There was no significant difference among remitters and nonremitters based on trauma subtypes. At baseline, CTQ scores had a significant influence on remission at 1 year (χ2 (1) = 5.57; p < .05). We lost this influence adding MADRS scores at baseline in the model (p = .063). CONCLUSION: We highlighted a significant association between the severity of depressive disorders and childhood maltreatment in the TRD population. Information about a history of childhood maltreatment helps in identifying individuals who could be less likely to go into remission after treatment.

Clinicians' Concerns About Mobile Ecological Momentary Assessment Tools Designed for Emerging Psychiatric Problems: Prospective Acceptability Assessment of the MEmind App.

BACKGROUND: Many mental disorders are preceded by a prodromal phase consisting of various attenuated and unspecific symptoms and functional impairment. Electronic health records are generally used to capture these symptoms during medical consultation. Internet and mobile technologies provide the opportunity to monitor symptoms emerging in patients' environments using ecological momentary assessment techniques to support preventive therapeutic decision making. OBJECTIVE: The objective of this study was to assess the acceptability of a Web-based app designed to collect medical data during appointments and provide ecological momentary assessment features. METHODS: We recruited clinicians at 4 community psychiatry departments in France to participate. They used the app to assess patients and to collect data after viewing a video of a young patient's emerging psychiatric consultation. We then asked them to answer a short anonymous self-administered questionnaire that evaluated their experience, the acceptability of the app, and their habit of using new technologies. RESULTS: Of 24 practitioners invited, 21 (88%) agreed to participate. Most of them were between 25 and 45 years old, and greater age was not associated with poorer acceptability. Most of the practitioners regularly used new technologies, and 95% (20/21) connected daily to the internet, with 70% (15/21) connecting 3 times a day or more. However, only 57% (12/21) reported feeling comfortable with computers. Of the clinicians, 86% (18/21) would recommend the tool to their colleagues and 67% (14/21) stated that they would be interested in daily use of the app. Most of the clinicians (16/21, 76%) found the interface easy to use and useful. However, several clinicians noted the lack of readability (8/21, 38%) and the need to improve ergonometric features (4/21, 19%), in particular to facilitate browsing through various subsections. Some participants (5/21, 24%) were concerned about the storage of medical data and most of them (11/21, 52%) seemed to be uncomfortable with this. CONCLUSIONS: We describe the first step of the development of a Web app combining an electronic health record and ecological momentary assessment features. This online tool offers the possibility to assess patients and to integrate medical data easily into face-to-face conditions. The acceptability of this app supports the feasibility of its broader implementation. This app could help to standardize assessment and to build up a strong database. Used in conjunction with robust data mining analytic techniques, such a database would allow exploration of risk factors, patterns of symptom evolution, and identification of distinct risk subgroups.

Ecological Assessment of Clinicians' Antipsychotic Prescription Habits in Psychiatric Inpatients: A Novel Web- and Mobile Phone-Based Prototype for a Dynamic Clinical Decision Support System.

BACKGROUND: Electronic prescribing devices with clinical decision support systems (CDSSs) hold the potential to significantly improve pharmacological treatment management. OBJECTIVE: The aim of our study was to develop a novel Web- and mobile phone-based application to provide a dynamic CDSS by monitoring and analyzing practitioners' antipsychotic prescription habits and simultaneously linking these data to inpatients' symptom changes. METHODS: We recruited 353 psychiatric inpatients whose symptom levels and prescribed medications were inputted into the MEmind application. We standardized all medications in the MEmind database using the Anatomical Therapeutic Chemical (ATC) classification system and the defined daily dose (DDD). For each patient, MEmind calculated an average for the daily dose prescribed for antipsychotics (using the N05A ATC code), prescribed daily dose (PDD), and the PDD to DDD ratio. RESULTS: MEmind results found that antipsychotics were used by 61.5% (217/353) of inpatients, with the largest proportion being patients with schizophrenia spectrum disorders (33.4%, 118/353). Of the 217 patients, 137 (63.2%, 137/217) were administered pharmacological monotherapy and 80 (36.8%, 80/217) were administered polytherapy. Antipsychotics were used mostly in schizophrenia spectrum and related psychotic disorders, but they were also prescribed in other nonpsychotic diagnoses. Notably, we observed polypharmacy going against current antipsychotics guidelines. CONCLUSIONS: MEmind data indicated that antipsychotic polypharmacy and off-label use in inpatient units is commonly practiced. MEmind holds the potential to create a dynamic CDSS that provides real-time tracking of prescription practices and symptom change. Such feedback can help practitioners determine a maximally therapeutic drug treatment while avoiding unproductive overprescription and off-label use.

Fundamentals for Future Mobile-Health (mHealth): A Systematic Review of Mobile Phone and Web-Based Text Messaging in Mental Health.

BACKGROUND: Mobile phone text messages (short message service, SMS) are used pervasively as a form of communication. Almost 100% of the population uses text messaging worldwide and this technology is being suggested as a promising tool in psychiatry. Text messages can be sent either from a classic mobile phone or a web-based application. Reviews are needed to better understand how text messaging can be used in mental health care and other fields of medicine. OBJECTIVE: The objective of the study was to review the literature regarding the use of mobile phone text messaging in mental health care. METHODS: We conducted a thorough literature review of studies involving text messaging in health care management. Searches included PubMed, PsycINFO, Cochrane, Scopus, Embase and Web of Science databases on May 25, 2015. Studies reporting the use of text messaging as a tool in managing patients with mental health disorders were included. Given the heterogeneity of studies, this review was summarized using a descriptive approach. RESULTS: From 677 initial citations, 36 studies were included in the review. Text messaging was used in a wide range of mental health situations, notably substance abuse (31%), schizophrenia (22%), and affective disorders (17%). We identified four ways in which text messages were used: reminders (14%), information (17%), supportive messages (42%), and self-monitoring procedures (42%). Applications were sometimes combined. CONCLUSIONS: We report growing interest in text messaging since 2006. Text messages have been proposed as a health care tool in a wide spectrum of psychiatric disorders including substance abuse, schizophrenia, affective disorders, and suicide prevention. Most papers described pilot studies, while some randomized clinical trials (RCTs) were also reported. Overall, a positive attitude toward text messages was reported. RCTs reported improved treatment adherence and symptom surveillance. Other positive points included an increase in appointment attendance and in satisfaction with management and health care services. Insight into message content, preventative strategies, and innovative approaches derived from the mental health field may be applicable in other medical specialties.

[The resilient elderly person]. / Le sujet âgé resilient.

Ageing requires a time of adaptation necessary for a person's loved ones and the environment, as well as the ageing body. Changes are imposed which require a new psychological energy to counter the losses and sometimes the traumas. Communicating in order to create a certain amount of resilience is one of the challenges of geriatric psychiatry.

Prevalence of antiphospholipid antibodies in psychiatric patients users and non-users of antipsychotics.

Past reports have suggested that antiphospholipid (aPL) antibodies may emerge as a response to antipsychotics treatment, as a high prevalence of aPL antibodies in antipsychotics users has been observed. However, no control group of non-medicated psychiatric patients was included in these reports. In a cross sectional study we determined the prevalence of aPL antibodies in 333 psychiatric inpatients. We compared the proportions of positive aPL antibodytests between users and non-users of antipsychotics with adjustments for potential confounders. The proportion of antipsychotics users carrying at least one aPL antibody ranged from 10·8% to 27·0% compared with 6·8% to 27·2% in non-users (P = 0·24, P = 0·24) depending on the method of detection of lupus anticoagulant (LA). The prevalence of LA detected by dilute Russell viper venom time or partial thromboplastin time-LA was not different between antipsychotics users and non-users (8·1% vs. 5·4%, P = 0·53 and 18·4% vs. 18·2%, P = 0·22), as well as the prevalence of IgM and IgG anti-ß2-glycoprotein-I antibodies, IgM and IgG anti-cardiolipin antibodies(3·8% vs. 2·0%, P = 0·75, 0·0% vs. 0·0%, P = not applicable, 1·1 vs. 1·4%, P = 0·91, 2·7% vs. 3·4%, P = 0·71). In conclusion, aPL antibodies were frequently found in patients with psychiatric diseases and no significant increase in the prevalence of aPL antibodies was observed in antipsychotics users.

SIAM (Suicide intervention assisted by messages): the development of a post-acute crisis text messaging outreach for suicide prevention.

BACKGROUND: Suicidal behaviour and deliberate self-harm are common among adults. Research indicates that maintaining contact either via letter or postcard with at-risk adults following discharge from care services can reduce reattempt risk. Feasibility trials demonstrated that intervention through text message was also effective in preventing suicide repetition amongst suicide attempters. The aim of the current study is to investigate the effect of text message intervention versus traditional treatment on reducing the risk of suicide attempt repetition among adults after self-harm. METHODS/DESIGN: The study will be a 2-year multicentric randomized controlled trial conducted by the Brest University Hospital, France. Participants will be adults discharged after self-harm, from emergency services or after a short hospitalization. Participants will be recruited over a 12-month period. The intervention is comprised of an SMS that will be sent at h48, D7, D15 and monthly. The text message enquires about the patients' well-being and includes information regarding individual sources of help and evidence-based self help strategies. Participants will be assessed at the baseline, month 6 and 13. As primary endpoint, we will assess the number of patients who reattempt suicide in each group at 6 months. As secondary endpoints, we will assess the number of patients who reattempt suicide at 13 month, the number of suicide attempts in the intervention and control groups at 6 and 13 month, the number of death by suicide in the intervention and control groups at month 6 and 13. In both groups, suicidal ideations, will be assessed at the baseline, month 6 and 13. Medical costs and satisfaction will be assessed at month 13. DISCUSSION: This paper describes the design and deployment of a trial SIAM; an easily reproducible intervention that aims to reduce suicide risk in adults after self-harm. It utilizes several characteristics of interventions that have shown a significant reduction in the number of suicide reattempts. We propose to assess its efficacy in reducing suicide reattempt in the suicide attempter (SA) population. TRIAL REGISTRATION: The study was registered on Clinical Trials Registry (clinicaltrials.gov): NCT02106949, registered on 06 June 2014.

Evaluation of GPs diagnostic knowledge and treatment practice in detection and treatment of early schizophrenia: a French postal survey in Brittany.

AIMS: Evaluating French general practitioners (GPs) diagnostic knowledge and practice in the detection and treatment of early schizophrenia as well as needs and preferences with specialist services. METHODS: A postal survey comprising 27 questions was conducted among 2,039 GPs from three counties of Western France. Composite scores were calculated to determine a level of diagnostic knowledge. RESULTS: A total of 515 GPs (25.3%) responded to the survey. The mean score to determine a level of knowledge on the most important aspects in detecting early stages of schizophrenia was 5.3 ± 2.50 [median = 6 (range 0-10)]. The mean score to determine the overall knowledge of schizophrenia was 8.1 ± 2.98 [median = 8 (range 1-16)]. The majority of surveyed GPs (76.1%) would treat early schizophrenia pharmacologically. A majority of GPs (53.9%) advise an insufficient duration of anti-psychotic treatment for first episode psychosis. The vast majority (90.8%) were in favour of a specialized outpatient service. CONCLUSIONS: French GPs tend to have a deficit in diagnostic knowledge and practice in detection and treatment of early schizophrenia. It seems important to provide GPs with continuing medical education (CME) on detection and management of early schizophrenia and to set up relevant specialized outpatient services.

[Suicide crisis, psychological suffering and advanced age]. / Crise suicidaire, souffrance psychique et avancée en âge.

Bound to the idea of a crisis and the brutal intrusion of psychological suffering, the suicide drama rarely lends itself to a direct analysis which can highlight the different stages of its process. Taking into account increasing quantities of scientific data from current research and the spirit of crisis interventions is fundamental for allowing hopes of effective prevention. Speaking the same language by using the same conceptual basis, that of the suicide crisis, is a prerequisite in pedagogical terms for the current care management of suicidal patients.

[Global approach to mental healthcare for the elderly]. / Abord global de la santé mentale du sujet âgé.

Mental health must be distinguished from the medical discipline of psychiatry, especially with regard to elderly patients, for whom, all too often, the care approach consists in admission to an institution. All sectors of psychiatry must be concerned by the mental health of the elderly.

[Acute and transient psychotic disorder at the onset of schizophrenia]. / La bouffée délirante aiguë au début de la schizophrénie.

Although the mode of onset of schizophrenia can be acute, it is important to remember that the disorder rarely starts as a "clap of thunder in a quiet sky", and that it is more often gradual and insidious, with negative and affective symptoms. Acute and transient psychotic disorder, on the other hand, is a short delusional episode forming suddenly and lasting a few days, sometimes a few hours. Schizophrenic evolution forms only part of the possible evolutions. It is therefore necessary to disassociate acute and transient psychotic disorder from schizophrenic disorders, which gives a wrong representation of the onset of schizophrenia.

Effect of early intervention for early-stage psychotic disorders on suicidal behaviours - a systematic review protocol.

Background: The early stages of psychotic disorders correspond to the early phases of the disease and include the prodromal phase and first-episode psychosis; they constitute a period at high risk of suicidal behaviour. A long duration of untreated psychosis (DUP) is among the risk factors of suicidal behaviour identified in this early period. Many studies have shown the effectiveness of early interventions on the overall prognosis of psychotic disorders in the early stages, and early intervention strategies have been developed and tested worldwide. Several authors reported an improvement in suicidal behaviours; however, all these data have not been systematically analysed yet. The main objective of this systematic review was to collect evidence on the effect on suicidal behaviour of early interventions for patients in the early stages of psychotic disorders. Methods: We will carry out a systematic review of the literature according to the PRISMA criteria by searching articles in five databases (PubMed, Cochrane, PsycINFO, Scopus, EMBASE), without restriction on the publication date. The selection criteria are: articles (any type; e.g. prospective, retrospective, controlled or uncontrolled, and literature reviews) on early interventions for psychotic disorders in the early stages with data on suicide attempts, death by suicide, suicidal ideation; articles written in English or French. Exclusion criteria are: articles on suicidal behaviours in patients with psychotic disorders in the early stages, but without early intervention, and articles on early-stage psychotic disorders without data on suicidal behaviours. Discussion: If this review confirms the effectiveness on suicidal behaviours of early interventions for young patients with psychotic disorders, the development/implementation of such intervention programmes should be better promoted. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42021237833.

Indirect effect of impulsivity on suicide risk through self-esteem and depressive symptoms in a population with treatment-resistant depression: A FACE-DR study.

INTRODUCTION: Suicide is a major health issue. Its prevalence is particularly high in subjects presenting major depression disorder (MDD), making this a key suicide-related risk factor. Suicide attempts in severe forms of MDD were assumed to be linked to impulsivity and loss of control. Nevertheless, we failed to find data specifically investigating the link between impulsivity and suicide risk in treatment-resistant depression (TRD). This study seeks to review this relationship. METHOD: Patients were recruited for a prospective cohort. Suicide risk and impulsivity were assessed using the International Neuropsychiatric Interview and Barratt Impulsiveness Scale, Version 10, respectively, while the severity of depressive symptoms was assessed using the Montgomery-Asberg Depression Rating Scale, anxiety with the State-Trait Anxiety Inventory and childhood maltreatment using the Childhood Trauma Questionnaire. RESULTS: 220 TRD patients were enrolled in the study. The impulsivity score was correlated with self-esteem, marital status, professional status and anxiety. There was no direct link to suicide risk. However, impulsivity was associated with self-esteem (coefficient: -0.24; p value 0.043) and depressive symptom severity (coefficient: 0.; p value 0.045). The suicide risk was significantly correlated with depressive symptom severity (coefficient = 0.38, p < 0.001) and self-esteem (coefficient = -0.34, p = 0.01). Considering these correlations, we postulated that the effect of impulsivity on suicide risk could be mediated by self-esteem in terms of depressive symptom severity and we finally found a relevant mediation model within impulsivity having an indirect effect on suicide risk by impacting self-esteem and depressive symptoms with anxiety also playing a significant role as a covariable. CONCLUSION: We found that impulsivity could play an indirect role with the involvement of self-esteem and depressive symptoms and the contributing role of anxiety.

Refining criteria for a neurodevelopmental sub-phenotype of bipolar disorders: a FondaMental Advanced Centers of Expertise for Bipolar Disorders study.

BACKGROUND: Bipolar disorder (BD) is a complex and heterogeneous psychiatric disorder. Neurodevelopmental factors were suggested to contribute to the etiology of BD, yet a specific neurodevelopmental phenotype of the disorder remains unidentified. Our objective was to define and characterize a neurodevelopmental phenotype (NDP) in BD and validate its associations with clinical outcomes, polygenic risk scores (PGS), and treatment responses. METHOD: We analyzed the FACE-BD cohort of 4,468 BD patients, a validation cohort of 101 BD patients, and two independent replication datasets of 274 and 89 BD patients. Using factor analyses, we identified a set of criteria for defining NDP. We next developed a scoring system for NDP-load and assessed its association with prognosis, neurological soft signs, polygenic risk scores for neurodevelopmental disorders, and responses to treatment using multiple regressions, adjusted for age and sex with bootstrap replications. RESULTS: Our study established a NDP in BD consisting of nine clinical features: advanced paternal age, advanced maternal age, childhood maltreatment, attention deficit hyperactivity disorder (ADHD), early onset of BD, early onset of substance use disorders, early onset of anxiety disorders, early onset of eating disorders, specific learning disorders. Patients with higher NDP-load showed a worse prognosis and increased neurological soft signs. Notably, these individuals exhibited a poorer response to lithium treatment. Furthermore, a significant positive correlation was observed between the NDP-load and PGS for ADHD suggesting potential overlapping genetic factors or pathophysiological mechanisms between BD and ADHD. CONCLUSIONS: The proposed NDP constitutes a promising clinical tool for patient stratification in BD.