A 10-15 years decrease in life expectancy has been observed in individuals with bipolar disorder (BD) and has been associated with premature cellular aging, but mechanisms involved remain unclear. Our team recently identified a subgroup of young individuals with prematurely shortened telomere length (TL).

The aims of the present study were to replicate this observation in a larger sample and to analyze the expression levels of genes associated with age or TL in a subsample of these individuals.

TL was measured by qPCR using peripheral blood DNA from 542 individuals with BD. Clustering analyzes were performed with age and TL as classification variables to identify similar groups.

Gene expression of 29 genes, including 20 associated with age and 9 with TL, was analyzed by RT-qPCR using peripheral blood RNA in a subgroup of 129 individuals. Gene expressions were compared between groups obtained from the previous clustering analyzes by Kruskal-Wallis and Mann-Whitney tests.

Clustering analyzes identified 3 subgroups and replicated the clustering previously described: a subgroup of aged individuals with a low TL (mean age : 51.73 years ; mean TL : 2), a subgroup of young individuals with a high TL (mean age : 29.02 years ; mean TL : 4.36) and a subgroup of young individuals but with a low TL (mean age : 29.64 years ; mean TL : 1.96). None of the tested clinical variables were significantly associated with this subgroup.

Furthermore, gene expression level analyzes showed that only POT1 expression was different between the two subgroups of young individuals, with a downregulation of POT1 expression in the subgroup with a lower TL level. POT1 is a protein involved in the maintenance of TL. POT1 binds to another protein TPP1 allowing the recruitment of telomerase, the enzyme which extends TL. Our hypothesis is that in the subgroup presenting a lower POT1 expression, the POT1-TPP1 complex cannot form and thus prevents telomerase recruitment and TL elongation.

This study confirms, on a larger sample, the existence of a subgroup of young individuals with BD presenting accelerated cellular aging. The observed decrease of POT1 expression level suggests a newly described cellular mechanism in individuals with BD, that may contribute to telomere shortening.

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Migraine and bipolar disorder (BD) are two chronic and recurrent disorders with a major impact on patient’s quality of life. It is now well known that affective disorders and migraine are often comorbid (Leo et al. Scand J Pain. 2016; 11:136-145). Starting from these observations, we can hypothesis that BD patients with comorbid migraine might have specifical clinical and biological features.

The aim of this study was to estimate the prevalence of migraine in a cohort of French BD patients; determine sociodemographic, clinical, and biological features associated BD-migraine comorbidity.

4348 BD patients from the FACE-BD cohort were included from 2009 to 2022. Sociodemographic and clinical characteristics, lifestyle information, and data on antipsychotic treatment and comorbidities were collected, and a blood sample was drawn. The Structured Clinical Interview for DSM-IV Axis I Disorders was used to confirm the diagnosis of BD. Migraine diagnosis was established according to a clinician-assessed questionnaire.

20.1% of individuals with BD had comorbid migraine. Half of these patients received treatment for migraine. Multivariate logistic regression model showed that risk of migraine in women was nearly twice that in men (OR = 1.758; 95% CI, 1.345-2.298). Anxiety disorder, sleep disturbances and childhood trauma were also associated with an increased risk of migraine comorbidity. Patients receiving antipsychotic treatment had less risk of developing migraine than those not receiving those treatment (OR 0.716, 95% CI, 0.554-0.925), independent of other potential confounders.

The prevalence of migraine in our cohort was lower than those previously reported in other studies. This result might suggest an overestimation of migraine diagnosis in BD patients population studies. However, BD-migraine comorbidity could constitute a subphenotype of bipolar disorder requiring specific treatments.

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Treatment resistant depression (TRD) affects a substantial proportion of patients with depression and carries a large unmet need. Esketamine nasal spray (NS), in combination with a selective serotonin reuptake inhibitor (SSRI) or serotonin norepinephrine reuptake inhibitor (SNRI), has been shown to reduce depressive symptoms and risk of relapse, in patients with TRD (Popova, V., et al. 2019. Am J Psychiatry; Daly, E.J., et al. 2019. JAMA Psychiatry). Esketamine NS has been authorised by European Medicines Agency as treatment for resistant depression since December 2019. ESKALE, is the first French observational study to describe TRD patients treated with Esketamine NS under real-world settings and to provide data on this innovative solution for patients.

To describe patients with TRD at Esketamine NS initiation and during the following 12-month period in real-world clinical practice.

ESKALE is a French, observational, multicentre, retrospective study of adult patients with moderate to severe TRD defined as a non-response to ≥ 2 oral antidepressant. Each patient was included in one of the 3 cohorts according to Esketamine NS start date: Temporary Authorisation for Use (ATUc) cohort, post-ATU cohort or post-launch period cohort. Data were collected from medical records of patients treated with Esketamine NS between 10-29-2019 and 06-14-2022. Primary objective is to describe patients’ profile and Esketamine NS conditions of use at esketamine initiation and during the 12-month period after esketamine initiation in real-world clinical practice (either patient had stop or not the treatment). Secondary objectives are to describe Esketamine NS management, safety profile and patient pathway.

Two standard descriptive statistical interim analysis were conducted and published in several conferences (Samalin L, et al. Presented at EPA Hybrid congress June 2022. P.2482; Samalin L, et al. Presented at ECNP Vienna, October 2022. P.0122). This final analysis describes the data collected from medical records of patients included in the study from 04-08-2020 to 06-30-2021. 157 patients were included from 26 French centers, the majority (>65%) of patients were females. Average age was 49 years old with 27 patients > 65 years old. Duration of the current depressive episode was up to 2,5 years (mean) with an average of more than three episode in the patient’s entire life (mean). At esketamine initiation, 3 patients out of 4 were clinically perceived to have severe depression with a MADRS score of 32.0 (median). Patients had mainly depression with anxious distress specifier. Esketamine NS dose at initiation was mainly 56mg.

Eskale is the first French cohort study generating real-world evidence on treatment resistant depression patients treated with Esketamine nasal spray. Results of the final analysis confirmed the 2 interim analysis results already published.

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Bipolar Disorder (BD) is a common psychiatric disease. It has been demonstrated a long time ago that bipolar patients are more painful than the healthy subjects. Substance use disorder is a frequent comorbidity in BD, but also in painful patients. The aim of our study was to analyze if bipolar patients with a painful expression have more substance use disorder than bipolar patients without pain.

The aim of our study was to analyze if bipolar patients with a painful expression have more substance use disorder than bipolar patients without pain

We included all bipolar patients from the FACE-BD cohort which is a prospective cohort of French outpatients with BD enrolled at the 12 advanced Centers of Expertise in Bipolar Disorder (CEBD). Pain has been evaluated by the “pain item” of the EQ-5D scale and we divided subjects in four categories: “no pain”, “slight pain”, “moderate pain”, “severe or extreme pain”. A multivariate analysis was performed to identify differences between each pain’s groups according to the kind of substance use disorder, psychiatric comorbidities and clinicals data.

The cohort enrolled 1897 bipolar patients, 970 had no pain (51.1%), 507 had slight pain (26.7%), 298 had moderate pain (15.7%) and 122 had severe or extreme pain (6.4%). We found significant differences according to age, comorbidities and clinicals data with older, more anxious, and more severe patients more represented in the more painful groups. Painful bipolar patients had also more frequently lifetime substance use disorders (alcohol, opioid, sedative, marijuana) and we were able to characterize different profiles in bipolar patients.

Bipolar patients with a painful expression had more risks to have a lifetime substance use disorder, an anxiety disorder, and a higher score on MADRS. Interestingly, subjects seemed to prefer substances with anxiolytic or antalgic effects during the acute intoxication as alcohol, marijuana, opioid and sedatives.

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Évaluer l’efficience du palmitate de palipéridone (PP) par rapport aux antipsychotiques les plus communément utilisés en France.

Un modèle médico-économique a été développé afin de simuler la progression d’une cohorte de patients atteints de schizophrénie à travers quatre états de santé (« Stable-traité », « Stable-non-traité », « En-rechute », « Décédé »). PP a été comparé à rispéridone injectable à libération prolongée (ILP), aripiprazole ILP, olanzapine ILP, halopéridol décanoate et olanzapine orale (OO). Les coûts, les années de vie pondérées par la qualité de vie (« Quality-adjusted-life-year » ; QALY) et le nombre de rechutes ont été estimés sur cinq ans selon une perspective tous payeurs. Supposés stabilisés suite à une décompensation clinique, les patients initiaient un antipsychotique et passaient en phase de prévention de la rechute en cas de succès après trois mois. Ils/elles pouvaient arrêter leur traitement après une rechute, un manque de tolérance ou par choix, et passer sur la ligne de traitement suivante jusqu’à la troisième ligne (c.-à.-d. clozapine). Afin de prendre en compte l’observance, les probabilités de rechute en phase de prévention ont été calculées à partir de taux d’hospitalisation sur des données françaises en vie réelle. Les données de tolérance et d’utilité ont été dérivées d’études internationales, et les coûts de sources françaises. La robustesse des résultats a été testée via des analyses de sensibilité.

À 5 ans, PP est le moins coûteux des ILP et est associé à un surcoût de 249 € par rapport à OO. Rispéridone ILP et PP sont associés aux plus grands nombres de QALY. PP domine tous les autres ILP en termes de rechute évitée hormis olanzapine ILP.

PP est le moins coûteux des antipsychotiques ILP en France. OO est l’antipsychotique le moins coûteux, mais est associée à un nombre plus faible de QALY gagnées et de rechutes évitées comparé aux antipsychotiques ILP.

As part of a process to improve bipolar disorders (BPD) treatment and outcome in France, AFBP developed recommendations in the management of patients with bipolar disorders for French practitioners. The recommendations aim to reflect both evidence-based practice and real-world experience. Here, we will focus on the management of BPD with comorbid addictive disorders.

A formalized method by expert consensus panel was used. 239 questions were developed and sent to a panel of 40 French experts in order to assess six domains:

1. 1) screening and diagnosis,

2. 2) acute phase treatment,

3. 3) maintenance and non pharmacological treatment,

4. 4) somatic comorbidities,

5. 5) psychiatric comorbidities and suicide risk management and

6. 6) special populations.

Special attention was made to situations where evidence based treatment are lacking.

The treatment of BPD and comorbid addictive disorders should be concurrent. The only exception is during an alcohol withdrawal where mood state may be reassessed for a second time. Experts recommend the use of atypical antipsychotics or anticonvulsants during a manic, mixed or depressive episode as well as in prophylaxia. During a depressive episode, the adjunction of an antidepressant may be considered. If adjunctive sedative treatment is necessary, a sedative classical antipsychotic seems to be a better choice that benzodiazepine. Substitution treatment for opioid must not be stopped. A psychotherapy focused on the addiction should be systematic in susbtance dependence and proposed in substance abuse.

The French expert panel recommends different therapeutic options for patients with dual diagnosis compared to usual BPD patients.

The method chosen for these guidelines is a formalized consensus of experts. It enables, through a series of specific clinical situations proposed to the experts, to provide recommendations for the management of bipolar disorder. The situations where defined because they are not associated to evidence-based recommendations according to the lack of controlled studies.

40 experts participate to this consensus. As in most of the guidelines for the treatment of bipolar disorder, more than 50 % of experts (51,3 to 72,9%) recommend the same therapeutic strategies to treat major depressive episode whichever the type (bipolar I or II).

Unlike to other guidelines, French experts propose different therapeutic according to the presence or absence of rapid cycling. For major depressive episode without rapid cycling, 63% experts recommend a combination of an antidepressant with a mood stabilizer. In rapid cyclers, 51% experts recommend the use of a mood stabilizer in monotherapy or in combinaison, but never associated with antidepressant.

This methodological approach enables to get closer to everyday clinical practice and integrate specificities of prescription through a national panel of experts. On the other hand, this type of methodology highlights the research perspectives: i.e. management of acute depression with rapid cycle in bipolar disorder.

In schizophrenia, depot formulations are not widely used in everyday practice. Clinicians’ attitudes play a major role in this low level of use of Long Acting Injectable (LAI). As a consequence, only 35% of patients declare to be well- informed about those formulations.

This study aims to assess psychiatrists’ attitudes toward the use of long-acting injectable antipsychotics in schizophrenia.

During the French Congress of Psychiatry (November 2010, Lyon), we interviewed 113 psychiatrists about the factors that influenced their prescription of LAI. We used a structured interview, adapted from the two questionnaires developed by Heres et al. in two studies about the attitudes of German Psychiatrists. Multidimensional and cluster analyses were performed to identify correlations.

Hazard risk for others, depot experienced, non-compliance and relapse in the past incited psychiatrists to prescribe LAI antipsychotic. Two different clusters of patients were identified: cluster I corresponded to patients with a past history of relapse and poor compliance and cluster II corresponded to patients with a high level of insight and of therapeutic alliance. The most important factor against the use of LAI was a sufficient estimated compliance with the oral formulation. The risk of extrapyramidal symptoms is, in our sample, one of the main reasons for a limited use of depot neuroleptic.

Most factors influencing clinicians’ attitudes toward the use of LAI are shared in many countries. Some attitudes related to organisational aspects, particularly the relevance of healthcare costs may vary from one country to another.

Residual symptoms (RS) are common in bipolar disorder. There is no clear consensus on how RS are defined, and individual clinicians may have their own perceptions of this clinical problem.

The aim of this study is to define RS and to describe their management using a qualitative analysis.

A qualitative study was conducted. Data were collected from five focus groups including 41 psychiatrists all over France. An interview guide was used, including questions about definition of RS, their assessment and influence on the management of bipolar patients. Content analysis was used to identify themes emerging from the focus groups.

There was no consensus among participants regarding an explicit definition of RS. The definition appears to be multifactorial, interactive and scalable. It is based both on the psychiatrist's therapeutic objectives and patient's complaints. Eight major RS was identified: suicidal risk, emotional dysregulation, compliance, cognitive impairment, sleep disorder, functional disability, complaints from the patients and the development of comorbidities.

Content analysis underlines the fact that: standardized tools are not used in clinical practice; RS are a constant preoccupation; they justify optimisation of medication and adjustment of visit frequency.

Qualitative study is helpful to define and describe RS. Identifying RS is an important way of achieving implementation strategies and improve management of bipolar patients.

As part of a process to improve the quality of care, the Association for Biological Psychiatry and Neuropsychopharmacology (AFPBN) developed recommendations for the use and management of Long Acting Injectable (LAI) Antipsychotics in clinical practice.

Based on a literature review, a written survey was prepared that asked about 539 options in 32 specific clinical situations. We contacted 64 national experts, 42 (65,6%) completed the survey. According to the answers for each situation based on a 9-points scale, a categorical rank (first-line/preferred choice, second-line/alternate choice, third-line/usually inappropriate) was assigned to each option. First-line option was defined as a strategy rated as 7–9 (extremely appropriate) by at least 50% of the experts.

For French experts, LAI Antipsychotics are indicated in patients with schizophrenia, schizoaffective disorder and bipolar disorder. According to their efficacy and tolerability risperidone LAI then olanzapine LAI are recommended as first line for maintenance treatment in schizophrenia, even after the first episode. Depot neuroleptics are recommended as second line for maintenance treatment in schizophrenia. LAI Second Generation Antipsychotics are recommended as second line in bipolar disorder. Several clusters of patients are identified, characterizing a specific profile for the use of LAI. Recommendations for the use of LAI and switch from oral to injectable formulations are suggested.

The use of LAI has advantages as maintenance treatment but their prescription rate is generally below 30% in different countries. Specific guidelines for the use and management of this formulation could improve their use in clinical practice.

This study aimed at using latent variable modelling to explore the significantly contributing variables to functioning in schizophrenia patients.

The study cohort comprised 296 schizophrenia patients evaluated once for demographic characteristics, functioning (FROGS, SWN-K, QLS) and symptomatology (Positive and Negative Syndrome Scale [PANSS]). First exploratory multivariate analyses were conducted and then a model with functioning as a latent variable was proposed and tested with the data.

Symptomatology as negative, cognitive and excitation factor are significant predictors of functioning assessed through FROGS (P<0.0001), SWN-K and QLS (P<0.001). The model was constructed with functioning defined as a latent variable, indicators are subscores on FROGS, SWN-K, QLS and exogenous variable included symptomatology, Duration of Untreated Psychosis (DUP) and educational level.

Using the five clinical dimensions of the PANSS, (Positive, Negative, Cognitive, Anxiety/Depression and Excitation) the negative and cognitive dimensions are highly correlated via the latent variable to the three dimensions of functioning evaluated by the FROGS: “daily life”, “social functioning” and “treatment” and the QLS subscores (interpersonnal, common object, instrumental role). Educationnal level is positively linked to functioning but not DUP. The model emphasizes the need for treatment strategies that have an effect on cognitive-factors, to improve functioning in schizophrenia.

Despite a favorable pharmacological rational, the prescription of antipsychotics depot formulation in patients with schizophrenia is low.

The goal of our study was to assess the attitudes of French psychiatrists toward the use of depot antipsychotics in patients with schizophrenia.

113 french psychiatrists were interviewed at a congress of psychiatry, using a questionnaire to identify psychiatrists attitudes influencing the use of long-acting injectable antipsychotics (LAI) in schizophrenia. Multidimensional and cluster analyses were used to detect correlations.

According to data compiled by the german team of S. Heres (2008), two clusters of factors specific to the patient for the prescription of antipsychotic depot, have been identified: the cluster “high level of therapeutic alliance and high level of insight” on the one hand and the cluster “poor compliance to oral therapy and high number of relapses in the past” on the other. The most important factor against the use of LAI antipsychotics is a sufficient estimated compliance with the oral formulation. For first-generation LAI, the main factor is the risk of extra pyramidal symptoms and for second-generation LAI, it is the unavailability of the equivalent of oral formulation.

Among the reasons influencing the prescription of LAI antipsychotic, history of poor adherence to oral therapy is important. In contrast, the highlighting of a profile of patients with a high level of insight and a high level of therapeutic alliance, confirms the value of these forms beyond the traditional profile of non-adherent.

Deliberate self-harm (DSH) causes important concern in prison inmates as it worsens morbidity and increases the risk for suicide. The aim of the present study is to investigate the prevalence and correlates of DSH in a large sample of male prisoners.

A cross-sectional study evaluated male prisoners aged 18+ years. Current and lifetime psychiatric diagnoses were assessed with the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders - DSM-IV Axis I and Axis II Disorders and with the Addiction Severity Index-Expanded Version. DSH was assessed with The Deliberate Self-Harm Inventory. Multivariable logistic regression models were used to identify independent correlates of lifetime DSH.

Ninety-three of 526 inmates (17.7%) reported at least 1 lifetime DSH behavior, and 58/93 (62.4%) of those reported a DSH act while in prison. After multivariable adjustment (sensitivity 41.9%, specificity 96.1%, area under the curve = 0.854, 95% confidence interval CI = 0.811–0.897, P < 0.001), DSH was significantly associated with lifetime psychotic disorders (adjusted Odds Ratio aOR = 6.227, 95% CI = 2.183–17.762, P = 0.001), borderline personality disorder (aOR = 6.004, 95% CI = 3.305–10.907, P < 0.001), affective disorders (aOR = 2.856, 95% CI = 1.350–6.039, P = 0.006) and misuse of multiple substances (aOR = 2.024, 95% CI = 1.111–3.687, P = 0.021).

Borderline personality disorder and misuse of multiple substances are established risk factors of DSH, but psychotic and affective disorders were also associated with DSH in male prison inmates. This points to possible DSH-related clinical sub-groups, that bear specific treatment needs.

Most studies selected euthymic patients with bipolar disorder in inter-episodic phase according to clinical remission criteria at least between 1 and 6 months. However, possible differences can exist in the course of clinical symptoms in bipolar patients related to the duration of clinical remission.

The main aim of this study was to evaluate the clinical status of bipolar patients after 6 months of clinical remission.

We performed a cross-sectional study of bipolar outpatients in clinical remission for at least 6 months. Bipolar Depression Rating Scale (BDRS), Young Mania Rating scale, Pittsburgh Sleep Quality Index (PSQI) scale, Visual Analogic Scales (VAS) evaluated cognitive impairment were used to assess residual symptomatology of patients. Multivariate analysis (MANCOVA) was conducted for analysing possible differences between 3 groups of patients according to their duration of clinical remission (< 6 months–1 year, < 1 year–3 years, < 3 years–5 years).

A total of 525 patients were included into the study. The multivariate analysis indicated a significant effect of the duration of clinical remission on the different residual symptoms (Pillai's trace: F 4.48, P < 0.001). The duration of clinical remission was associated with the significant improvement of the BDRS total score (P = 0.013), the PSQI total score (P < 0.001) and the cognitive VAS total score (P < 0.001)

These results support a possible improvement of residual symptoms according to the duration of clinical remission in bipolar patients. Any definition of euthymia should specify the duration criteria.

The authors have not supplied their declaration of competing interest.

Alcohol use disorders and bipolar disorder commonly co-occur and both are associated with more pejorative outcomes, thus constituting a major public health problem. We undertook this synthetic review to provide an update on this issue in order to clarify the nature of the relationship between the two disorders, improve clinical outcomes, prevent complications and therefore optimize management of patients.

We conducted an electronic search by keywords in databases MEDLINE, EMBASE, PsychINFO, published in English and French from January1985 to December 2015.

The AUD prevalence is important among BD patients in whom the effects of alcohol are more severe. However, in terms of screening, it appears that the comorbidity is not systematically sought. The concept of co-occurrence finds its clinical interest in the development of specific screening and therapeutic strategies. To date, there are only few recommendations about the management of dual diagnosis and the majority of them support “integrated” approaches.

Recommendations should emphasize this strong co-occurrence and promote systematic screening and offered integrated cares.

The authors have not supplied their declaration of competing interest.

Euthymic patients with bipolar disorder (BD) experience residual symptoms. Interestingly, residual symptoms appear to impact the natural course of BD and represent potential predictors of recurrence and functional impairment.

The study aimed to analyse the relationship between residual depressive symptoms, sleep disturbances and cognitive impairment as determinants of psychosocial functioning in a large sample of euthymic BD patients.

We performed a cross-sectional study of 468 BD outpatients in clinical remission for at least 6 months. Bipolar Depression Rating Scale (BDRS), Pittsburgh Sleep Quality Index (PSQI) scale, Visual Analogic Scales (VAS) evaluated cognitive impairment and functioning assessment short test were used to assess residual symptomatology and functioning of patients. We evaluated functioning with. Structural equation modelling (SEM) was used to describe the relationships among the residual depressive symptoms, sleep disturbances, perceived cognitive performance and functioning.

SEM showed good fit. This model revealed that residual depressive symptoms (path coefficient = 0.37) and perceived cognitive performance (path coefficient = 0.27) were the most important features significantly related to psychosocial functioning. Sleep disturbances were indirectly associated with functioning via residual depressive symptoms and perceived cognitive performance (path coefficient = 0.23).

This study contributes to a better understanding of the determinants of psychosocial functioning during the interepisodic periods of BD patients. These findings should have implications for the improvement of functioning of BD patients in a personalized approach to treatment.

COI: Dr. Samalin reports personal fees and nonfinancial support from Astra-Zeneca, Bristol Myers Squibb, Janssen, Lundbeck, and Otsuka.

The authors L. Boyer, A. Murru, I. Pacchiarotti, M. Reinares, C.M. Bonnin, C. Torrent, V. Norma, P. Corinna, I. de Chazeron, M. Boucekine, P.A. Geoffroy, F. Bellivier, P.M. Llorca, E. Vieta have have not supplied their declaration of competing interest.