French Society for Biological Psychiatry and Neuropsychopharmacology (AFPBN) guidelines for the management of patients with partially responsive depression and treatment-resistant depression: Update 2024

International audienceIntroduction: The purpose of this update is to add newly approved nomenclatures and treatments as well as treatments yet to be approved in major depressive disorder, thus expanding the discussions on the integration of resistance factors into the clinical approach.Methods: Unlike the first consensus guidelines based on the RAND/UCLA Appropriateness Method, the French Association for Biological Psychiatry and Neuropsychopharmacology (AFPBN) developed an update of these guidelines for the management of partially responsive depression (PRD) and treatment-resistant depression (TRD). The expert guidelines combine scientific evidence and expert clinicians' opinions to produce recommendations for PRD and TRD.Results: The recommendations addressed three areas judged as essential for updating the previous 2019 AFPBN guidelines for the management of patients with TRD: (1) the identification of risk factors associated with TRD, (2) the therapeutic management of patients with PRD and TRD, and (3) the indications, the modalities of use and the monitoring of recent glutamate receptor modulating agents (esketamine and ketamine).Conclusion: These consensus-based guidelines make it possible to build bridges between the available empirical literature and clinical practice, with a highlight on the 'real world' of the clinical practice, supported by a pragmatic approach centred on the experience of specialised prescribers in TRD

Global and local cortical folding alterations are associated with neurodevelopmental subtype in bipolar disorders: a sulcal pits analysis

Background: Analyzing cortical folding may provide insight into the biological underpinnings of neurodevelopmental diseases. A neurodevelopmental subtype of bipolar disorders (BD-ND) has been characterized by the combination of early age of onset and psychotic features. We investigate potential cortical morphology differences associated with this subtype. We analyze, for the first time in bipolar disorders, the sulcal pits, the deepest points in each fold of the cerebral cortex. Methods: We extracted the sulcal pits from anatomical MRI among 512 participants gathered from 7 scanning sites. We compared the number of sulcal pits in each hemisphere as well as their regional occurrence and depth between the BD-ND subgroup (N = 184), a subgroup without neurodevelopmental features (BD, N = 77) and a group of healthy controls (HC, N = 251). Results: In whole brain analysis, BD-ND group have a higher number of sulcal pits in comparison to the BD group. The local analysis revealed, after correction for multiple testing, a higher occurrence of sulcal pits in the left premotor cortex among the BD-ND subgroup compared to the BD and the HC groups. Conclusion: Our findings confirm that BD-ND is associated with a specific brain morphology revealed by the analysis of sulcal pits. These markers may help to better understand neurodevelopment in mood disorder and stratify patients according to a pathophysiological hypothesis

Definition of early age at onset in bipolar disorder according to distinctive neurodevelopmental pathways: insights from the FACE-BD study

International audienceBackground: Converging evidence suggests that a subgroup of bipolar disorder (BD) with an early age at onset (AAO) may develop from aberrant neurodevelopment. However, the definition of early AAO remains unprecise. We thus tested which age cut-off for early AAO best corresponds to distinguishable neurodevelopmental pathways.Methods: We analyzed data from the FondaMental Advanced Center of Expertise-Bipolar Disorder cohort, a naturalistic sample of 4421 patients. First, a supervised learning framework was applied in binary classification experiments using neurodevelopmental history to predict early AAO, defined either with Gaussian mixture models (GMM) clustering or with each of the different cut-offs in the range 14 to 25 years. Second, an unsupervised learning approach was used to find clusters based on neurodevelopmental factors and to examine the overlap between such data-driven groups and definitions of early AAO used for supervised learning.Results: A young cut-off, i.e. 14 up to 16 years, induced higher separability [mean nested cross-validation test AUROC = 0.7327 (± 0.0169) for ⩽16 years]. Predictive performance deteriorated increasing the cut-off or setting early AAO with GMM. Similarly, defining early AAO below 17 years was associated with a higher degree of overlap with data-driven clusters (Normalized Mutual Information = 0.41 for ⩽17 years) relatively to other definitions.Conclusions: Early AAO best captures distinctive neurodevelopmental patterns when defined as ⩽17 years. GMM-based definition of early AAO falls short of mapping to highly distinguishable neurodevelopmental pathways. These results should be used to improve patients' stratification in future studies of BD pathophysiology and biomarkers

Subjects suffering from bipolar disorder taking lithium are less likely to report physical pain: a FACE-BD study

Introduction: Physical pain is a common issue in people with bipolar disorder (BD). It worsens mental health and quality of life, negatively impacts treatment response, and increases the risk of suicide. Lithium, which is prescribed in BD as mood stabilizer, has shown promising effects on pain.Methods: This naturalistic study included 760 subjects with BD (French FACE-BD cohort) divided in two groups: with and without self-reported pain (evaluated with the EQ-5D-5L questionnaire). In this sample, 176 subjects were treated with lithium salts. The objectives of the study were to determine whether patients receiving lithium reported less pain, and whether this effect was associated with the recommended mood stabilizing blood concentration of lithium.Results: Subjects with lithium intake were less likely to report pain (OR = 0.59, 95% CI [0.35-0.95]; p = 0.036) after controlling for sociodemographic variables, BD type, lifetime history of psychiatric disorders, suicide attempt, personality traits, current depression and anxiety levels, sleep quality, and psychomotor activity. Subjects taking lithium were even less likely to report pain when lithium concentration in blood was ≥0.5mmol/l (OR = 0.44, 95% CI [0.24-0.79]; p = 0.008).Discussion: This is the first naturalistic study to show lithium promising effect on pain in subjects suffering from BD after controlling for many confounding variables. This analgesic effect seems independent of BD severity and comorbid conditions. Randomized controlled trials are needed to confirm the analgesic effect of lithium salts and to determine whether lithium decreases pain in other vulnerable populations, such as people with chronic pain

Decreased telomere length in a subgroup of young individuals with bipolar disorders: replication in the FACE-BD cohort and association with the shelterin component POT1

Abstract Bipolar disorder (BD) has been associated with premature cellular aging with shortened telomere length (TL) as compared to the general population. We recently identified a subgroup of young individuals with prematurely shortened TL. The aims of the present study were to replicate this observation in a larger sample and analyze the expression levels of genes associated with age or TL in a subsample of these individuals. TL was measured on peripheral blood DNA using quantitative polymerase chain reaction in a sample of 542 individuals with BD and clustering analyses were performed. Gene expression level of 29 genes, associated with aging or with telomere maintenance, was analyzed in RNA samples from a subsample of 129 individuals. Clustering analyses identified a group of young individuals (mean age 29.64 years), with shorter TL. None of the tested clinical variables were significantly associated with this subgroup. Gene expression level analyses showed significant downregulation of MYC, POT1, and CD27 in the prematurely aged young individuals compared to the young individuals with longer TL. After adjustment only POT1 remained significantly differentially expressed between the two groups of young individuals. This study confirms the existence of a subgroup of young individuals with BD with shortened TL. The observed decrease of POT1 expression level suggests a newly described cellular mechanism in individuals with BD, that may contribute to telomere shortening