Catatonia is a severe psychomotor syndrome that occurs across psychiatric diagnoses and is increasingly conceptualized as reflecting neurodevelopmental vulnerability. The anterior cingulate cortex (ACC) plays a central role in motor initiation and cognitive-affective integration and displays substantial interindividual variability in its sulcal morphology, which is established prenatally and remains stable across life. In this MRI study, we examined whether ACC sulcal patterns represent a structural trait marker of catatonia. We analyzed high-resolution T1-weighted images from a hospital-based cohort comprising patients with catatonia (N = 109), psychiatric patients without catatonia (N = 323), and healthy controls (N = 91). The presence of the paracingulate sulcus (PCS) in each hemisphere was determined through blinded visual inspection, and regression analyses tested associations with diagnostic group, adjusting for age, sex, scanner type, intracranial volume, and benzodiazepine and antipsychotic exposure. Patients with catatonia exhibited a significantly reduced prevalence of the left PCS and diminished hemispheric asymmetry compared with both non-catatonic patients and healthy controls. These effects were independent of whether catatonia occurred within psychotic or mood disorders. PCS size did not differ across groups, and sulcal pattern did not correlate with catatonia severity among affected individuals. The findings demonstrate that ACC sulcal deviations are specifically associated with catatonia across diagnostic categories, supporting a neurodevelopmental etiology and reinforcing ACC involvement in its pathophysiology. Early-determined sulcal morphology may represent a trait-level marker contributing to vulnerability for catatonia, with implications for early identification, risk stratification, and targeted intervention strategies.

The human brain folds in utero, primarily during late gestation. Shortly after birth, cortical folding patterns are established and remain stable thereafter, making them promising early neurodevelopmental markers. Yet it is unclear whether representations given by current neuroimaging foundation models capture cortical folding variability. Here, we introduce Champollion, a self-supervised learning framework that learns interpretable local representations of cortical folding from structural MRI. Optimized on representative folding-related tasks, Champollion accurately captures known folding patterns across cortical regions and external datasets. In a comprehensive benchmark, it consistently outperforms neuroimaging and general-purpose foundation models. Furthermore, Champollion reveals richer genetic associations than conventional morphometric descriptors and identifies localized folding signatures associated with incomplete hippocampal inversion, prematurity, and maternal smoking. These results establish cortical folding as a rich and largely untapped source of neurodevelopmental information and illustrate how pre-processing and architectural inductive biases can recover biologically meaningful signals overlooked by current generalist foundation models.

Major depressive episode (MDE) is a common mental disorder that severely impacts patients’ lives and carries a high suicide risk. About 30% of patients are resistant to oral antidepressants, necessitating alternative approaches such as neurostimulation. The subcallosal cingulate (SCC), characterized by hyperactivity and altered functional connectivity (FC) in MDE, has emerged as a key target for interventions like deep brain stimulation (DBS) and transcranial focused ultrasound stimulation (TUS). Other techniques, including repetitive transcranial magnetic stimulation (rTMS) and electroconvulsive therapy (ECT), may influence SCC activity indirectly via network-level effects. We searched multiple databases for studies investigating changes in SCC connectivity following various neurostimulation techniques in depression. We included 28 studies using resting-state functional MRI to investigate SCC FC changes following neurostimulation for depression with different modalities: ECT, DBS, rTMS, tDCS, TUS. Results showed high variability across studies. rTMS targeting the DLPFC modulated SCC FC with the OFC, precuneus, and default mode network (DMN), while other targets affected connectivity with the hippocampus and supramarginal gyrus. Stronger baseline anticorrelation between SCC and DLPFC predicted better rTMS response. ECT studies reported heterogeneous effects, involving the temporal pole and vmPFC. TUS targeting SCC increased FC with the DLPFC, whereas TUS to the DLPFC enhanced FC between SCC subregions and mPFC or cerebellum. Findings remain heterogeneous, likely due to methodological inconsistencies, including variability in SCC ROI definitions and stimulation protocols. Standardizing analysis methods is essential to improve reproducibility and clarify the SCC’s role in treatment response.

Auditory–verbal hallucinations (AVHs) are among the most disabling symptoms of schizophrenia and often persist despite the use of adequate antipsychotic treatment. Conventional low-frequency repetitive transcranial magnetic stimulation (rTMS) targeting the T3P3 scalp site has demonstrated limited efficacy, likely due to interindividual variability in AVH-related brain networks. In this multicenter, randomized, double-blind phase 3 trial, 70 patients with drug-resistant AVHs received active 1-Hz rTMS targeted either with an individualized fMRI-based symptom-capture procedure or by using conventional T3P3 localization. fMRI-guided rTMS yielded a greater reduction in Auditory Hallucination Rating Scale (AHRS) scores at one month (mean difference, −5.43; 95% CI, −8.92 to −1.94), and the effects were sustained at three and six months. The number-needed-to-treat for neuroguided rTMS was 3.5. Clinical response was associated with greater E-field overlap with AVH-related networks. These findings demonstrate that fMRI-guided neuronavigation increases rTMS efficacy, thus supporting its use to optimize the treatment of drug-resistant AVHs in schizophrenia.

BACKGROUND AND HYPOTHESIS:Identifying reliable diagnostic biomarkers in catatonia remains a key challenge to improve early intervention and reduce morbidity and mortality. Since its pathophysiology may involve cortical dysconnectivity, electroencephalography (EEG) could provide accessible disease-associated measures, such as power spectral density (PSD), peak alpha frequency (PAF), and C and D microstates. However, EEG is yet to be used for this purpose. STUDY DESIGN:This study is a case-control retrospective transdiagnostic hospital-based cohort. We analyzed resting-state EEG data from patients diagnosed with schizophrenia or mood disorders, both with (n = 102) and without (n = 519) catatonia. Linear regression models assessed associations between catatonia status and PSD, PAF, and microstates, adjusting for age, sex, medication (computed as olanzapine, fluoxetine, and diazepam equivalents), and comorbid neurodevelopmental or neurological conditions. STUDY RESULTS:Patients with catatonia showed increased delta power (T = 2.37, PFDR = .03), decreased alpha power (T = -3.55, PFDR = .002) and increased gamma power (T = 3.14, PFDR = .008), reduced PAF (T = -2.60, P = .03), and longer mean duration of microstate C (T = 2.17, P = .03). CONCLUSIONS:Routine clinical EEG revealed quantitative neurophysiological differences between patients with and without catatonia in a transdiagnostic population with psychotic and mood disorders. PSD, alpha peak frequency, and microstate anomalies in catatonia shed light on its underlying pathophysiology, suggesting a probable neurodevelopmentally-related excitation/inhibition dysregulation. Importantly, this indicates that routine clinical EEG could be used for diagnostic biomarker development, which would ultimately improve early detection and treatment.

Introduction Electroconvulsive therapy (ECT) is the most effective intervention for depression, yet no validated biomarkers reliably predict which patients will remit. Large-scale structural and functional dysconnectivity is well-established in major depressive disorder, motivating the use of graph-theoretical metrics to capture network architecture and identify treatment-sensitive markers. Methods In a prospective longitudinal study, 41 adult patients with a major depressive episode undergoing ECT and 24 healthy controls underwent anatomical, diffusion and resting-state functional MRI at baseline (V1). Patients were reassessed after five ECT sessions (V2, n = 31) and two weeks following treatment completion (V3, n = 29). Structural networks were constructed from multi-shell diffusion tractography and functional networks from rs-fMRI. Longitudinal change of global and local efficiency was assessed using linear mixed-effects models, and baseline predictors of remission (MADRS ≤10 at V3) were evaluated using ANOVAs and penalized binomial regression. Results Graph-theory metrics remained stable across timepoints, indicating no large-scale network reorganization during ECT. At baseline, patients showed reduced structural local efficiency relative to controls. Future remitters exhibited lower structural local and global efficiency in fractional anisotropy and neurite density index (NDI)-weighted networks at baseline compared with non-remitters, whereas non-remitters showed reduced functional local efficiency at baseline relative to controls. Penalized regression identified baseline NDI-weighted global efficiency as a significant predictor of remission. Conclusion Baseline structural and functional network profiles distinguished ECT remitters from non-remitters. These findings suggest that non-remission is characterized by reduced functional integration with relatively preserved structural connectivity, while remission is associated with preserved functional organization but lower baseline structural efficiency.

Psychiatric disorders are common and can cause psychological disabilities. While the creation of day hospitals (DHs) was intended to direct psychiatric care towards community settings, they may have paradoxically contributed to a form of chronicity. Furthermore, the heterogeneity and lack of evaluation of care within DHs prevent the availability needed to collect objective data on users outcomes. In this article, we aim to describe and measure the effects of a transformation of practice within a sector-based DH initially focused on traditional institutional psychiatry towards a rehabilitation model of care which offers different therapeutic tools, structured in three stages, and whose main objective is professional integration. This retrospective mirror study compares, before and after the transformation of this DH, several indicators including the rate of professional integration and its maintenance after two years. We found that this psychosocial rehabilitation model for care allowed a very clear increase in the professional integration rate and its maintenance at two years while reducing the length of stay to around 18 months. These promising results therefore highlight the pivotal role of DHs as “stepping stones” in addressing psychological disabilities towards recovery.

BACKGROUND:Neurodevelopmental conditions are crucial risk factors for catatonia in pediatric and adult populations. Recent case reports and studies have identified an increasing number of genetic abnormalities likely contributing to catatonia. Catatonia associated with genetic abnormalities is challenging in terms of identification, chronicity, and resistance to treatment. In addition, understanding these genetic abnormalities through identifying rare single nucleotide and copy number variants may offer valuable insights into the underlying pathophysiology. METHODS:We conducted a systematic review of all genetic abnormalities reported with catatonia and performed a gene-set enrichment analysis. Our systematic literature search for relevant articles published through July 15, 2024, using combinations of "catatonia," "catatonic syndrome," "genetic," and "genes" in PubMed, yielded 317 articles. Of these, 94 were included, covering 374 cases of catatonia and 78 distinct genetic abnormalities. RESULTS:This review discusses the clinical presentation of catatonia for each genetic disorder, the treatment strategies, and the putative underlying mechanisms. CONCLUSIONS:The review highlights that catatonia underpinned by genetic abnormalities presents specific clinical and treatment-response features. Therefore, we propose genetic testing guidelines for catatonia and advocate for systematically investigating catatonia in several genetic diseases. Regarding the pathophysiology of catatonia, the gene ontology of biological processes reveals significant enrichment of variants in synaptic and post-synaptic regulatory genes, particularly within GABAergic neurons, reinforcing the implication of the excitatory/inhibitory imbalance. Finally, genetic variants are enriched in microglial cells, highlighting the role of brain inflammation in triggering catatonia. This comprehensive insight could pave the way for more effective management strategies for this condition.

This article reviews early studies that have demonstrated the ability of low intensity ultrasound waves to modulate brain activity. It also reviews the technological developments that have enabled transcranial ultrasound stimulation (TUS) to achieve millimetric spatial accuracy. This allows precise, noninvasive and reversible brain stimulation, a unique capability when compared to existing techniques such as transcranial magnetic stimulation, transcranial direct-current stimulation, and deep brain stimulation with implanted electrodes. TUS is now technologically ready for clinical translation. As psychiatric disorders have a high prevalence in the general population, and suffer from unmet noninvasive deep brain stimulation clinical needs, this article focuses on the potential application of TUS in psychiatry and reviews recently published clinical proofs of concept that have addressed depression, anxiety, schizophrenia and substance use disorders. Finally, the strengths and weaknesses of TUS technology are discussed, with reference to its clinical translation.

BACKGROUND:Neuromodulation of deep brain regions has shown promise for treatment-resistant depression (TRD). However, it currently requires neurosurgical electrode implantation, posing significant risks and limiting widespread use while TRD affects around 100 million people worldwide. Low-intensity transcranial ultrasound stimulation (TUS) could allow precise and non-invasive deep neuromodulation, provided that the challenge of the defocusing effects of the skull is tackled. OBJECTIVE/HYPOTHESIS:Here, we present the development of a portable and neuronavigated TUS prototype based on the use of patient-specific metamaterials (metalens) that correct for skull-induced aberrations. We then present the first application of metalens-based Transcranial Ultrasound Stimulation (mTUS) in TRD. The primary objective was to assess the safety and efficacy of mTUS targeting on individual level specific white matter tracts of the subcallosal cingulate involved in TRD. METHODS:The safety and precision of this device was addressed through a series of numerical simulations and experimental measurements on ex vivo human skulls. Five participants with TRD were included in this open-label study (ClinicalTrials.gov identifier: NCT06085950) and underwent an intensive 5-day course of mTUS with a total of 25 sessions of 5 min each. RESULTS:No serious adverse events occurred during the study. By day 5 of treatment, depression severity was reduced by an average of 60.9 % (range: [30 %-83.9 %]), and four out of five patients qualified as responders, with two of them in remission. CONCLUSIONS:This study provides first-in-human evidence of the potential of mTUS as a precise, safe and effective non-invasive neuromodulation technique for neuropsychiatric disorders involving deep brain regions, offering a safer and more accessible alternative to invasive approaches.

Introduction Electroconvulsive therapy (ECT) induces an increase in hippocampal volume presumed to reflect neurogenesis in severely depressed patients. We hypothesized that Neurite Orientation Dispersion and Density Imaging (NODDI) provides in vivo evidence of hippocampal neurogenesis following ECT. Methods This prospective longitudinal study included 43 depressed patients treated by ECT. Three sequential evaluations (V1: baseline, V2: at 2 weeks into ECT, V3: 14 days within completing ECT) included a 3T MR-scan with 3D T1-weighted and multi-shell diffusion (b = 200/1500/2500 s/mm2, 30/45/60 directions) sequences and clinical assessment with depression scales. Q-ball, Diffusion Tensor and NODDI models provided the following metrics: axial (AD), radial (RD) and mean diffusivity (MD), fractional anisotropy (FA) and generalized FA (GFA), neurite density index (NDI), isotropic fraction (Fiso), neurite orientation and dispersion index (ODI). FreeSurfer was used to extract whole hippocampal and subfields volumes from T1-weighted images. A linear mixed-effect model assessed the changes over time in hippocampal volumes and mean diffusion metrics, and their relationship with clinical response was analyzed with ANOVA. Bonferroni corrections were applied. Results 107 MRI were obtained at V1 (n = 43), V2 (n = 34) and V3 (n = 30) from 43 patients. Mean (± SD) interval between V1-V3 was 70 ± 25 days. Diffusion metrics in the hippocampus were: at V2, a decrease in left GFA, right AD, bilateral Fiso, and a bilateral ODI increase. Additionally, at V3, we observed a left MD decrease, bilateral AD decrease, right NDI increase, and bilateral ODI increase. Notably, NDI and Fiso changes were localized to the dentate gyrus but not to the hippocampal tail. ECT-responders showed a significant right hippocampus volume increase at 2 weeks into ECT. Conclusion After ECT, the observed increase in hippocampal volume is accompanied by bilateral changes in NODDI parameters, consistent with hippocampal neuroplasticity.

Introduction Severe depressive disorder is associated with smaller hippocampal volumes. We hypothesized that Neurite Orientation Dispersion and Density Imaging (NODDI) could provide in vivo evidence of decreased hippocampal neuroplasticity in patients with depression. Methods This cross-sectional study evaluated 43 patients with treatment-resistant depression eligible for electroconvulsive therapy and 24 controls. MRI evaluations included a 3T scan with 3DT1-weighted and multi-shell diffusion sequences (b = 200/1500/2500 s/mm², 30/45/60 directions). Q-ball, diffusion tensor, and NODDI models were used to obtain axial diffusivity (AD), radial diffusivity (RD), mean diffusivity (MD), fractional anisotropy (FA), generalized FA (GFA), neurite density index (NDI), isotropic fraction (Fiso), and orientation dispersion index (ODI). Hippocampal volumes were extracted using FreeSurfer from T1-weighted images. Pearson correlations adjusted for sex and group analyzed the relationship between age and bilateral hippocampal diffusion. Mixed-effects models assessed the impact of depression, hemisphere, sex, and age on eight diffusion metrics. Correlation matrices and group-specific correlograms analyzed diffusion metrics across both hippocampi. Principal component analysis (PCA) reduced these metrics to components explaining ‘95% of the variance. Results A total of 107 MRIs from patients and 24 MRIs from controls were analyzed. Hippocampal NDI was negatively correlated with age (r = -0.41, p = 0.002), while hippocampal Fiso was positively correlated (r = 0.45, p = 0.001). FA, GFA, AD, NDI, and ODI showed significant differences between patients and controls, despite comparable hippocampal volumes. PCA analysis effectively distinguished the two groups, achieving a diagnostic accuracy of 1. Conclusion Diffusion microstructural analyses reveal hippocampal alterations in severely depressed patients, potentially reflecting decreased neuroplasticity.

Catatonia is a severe psychomotor syndrome with high morbidity and mortality. Lorazepam and electroconvulsive therapy (ECT) are the main recommended treatments. Lorazepam-resistant catatonia accounts for about 30

The brain surface is composed of humps called gyri, separated by grooves called sulci. Although the main folds are common to all individuals, their shape varies, making them unique to each individual. Cortical folding may contain biomarkers that have yet to be deciphered. While conventional geometric approaches fail to fully characterize the high inter-individual variability, recent efforts in large-scale MRI data collection allow us to leverage the statistical power of deep neural networks. Here, we introduce Champollion V0, a self-supervised learning (SSL) algorithm to sort sulcal variability based on 21,070 subjects from the UKBioBank dataset. We revisit from scratch an existing model and optimize its ability to retrieve hand-labeled patterns defined by the neuroscientific community. Under linear evaluation on the latent space, Champollion V0 significantly improves the detection of three different kinds of folding patterns: the presence of a parallel sulcus (AUC increases from 73 R^2 increases on each of the six main geometric features), respectively in the cingulate, the orbital and the central region. These hand-labeled patterns were found to be correlated to neurodevelopmental pathologies. Champollion V0 could enable the automatic labeling of larger datasets for future studies. The code can be found on Github .

Over the past three decades, non-invasive brain stimulation (NIBS) techniques have gained worldwide attention and demonstrated therapeutic potential in various medical fields, particularly psychiatry. The emergence of these novel techniques has led to an increased need for robust training programs to provide practitioners, whether clinicians or scientists, with the necessary skills and knowledge. In response, a comprehensive training curriculum for NIBS in psychiatry has been developed in France. This curriculum was developed by a group of researchers and psychiatrists interested in the clinical application of NIBS in psychiatry, called STEP - Stimulation Transcranienne en Psychiatrie, under the auspices of the French Association of Biological Psychiatry. This perspective outlines the development and implementation of this course, tracing its inception, the evolution of the program, and the challenges encountered along the way. The position of the course in the national and international environment and its future prospects are also discussed. Through this perspective, we aim to summarize the collaborative efforts to promote NIBS teaching and research in French psychiatry.

L’électroconvulsivothe?rapie (ECT), traitement le plus efficace de la dépression pharmaco-résistante, induit une augmentation du volume hippocampique attribuée à une neurogénèse. Un modèle mutli-compartimental de diffusion comme NODDI (Neurite Orientation Dispersion and Density Imaging) permettrait d’étudier les modifications microstructurales hippocampiques ECT-induites. Étude prospective longitudinale monocentrique. 43 patients (26 femmes, 54.07 ans ± 18.09). Critères d'inclusion : dépression sévère (DSM-5) et indication d'ECT. Trois évaluations: initiale (V1), après 5 sessions d'ECT (V2), dans les 14 jours post-traitement (V3). Évaluation comprenant (1) IRM encéphalique 3T avec 3D SPGR T1 et diffusion multi-shell (b=200/1500/2500s/mm2, 30/45/60 directions, résolution 2mm isotropique), (2) scores de dépression dont MADRS. Extraction des (1) volumes hippocampiques par segmentation FreeSurfer des images T1 et (2) paramètres de diffusion régionaux avec la Ginkgo toolbox : diffusivités axiale, radiale et moyenne (DA, DR, DM), fraction d'anisotropie (FA), FA généralisée (GFA), isotropique (Fiso), index de densité de neurites (NDI) et d'orientation et dispersion des neurites (ODI). Modèle linéaire mixte évaluant les changements volumique et de diffusion hippocampiques (variables dépendantes), incluant sexe, volume initial (facteurs inter-sujets) et temps (intra-sujet). ANOVA pour étude de corrélation avec réponse/sévérité clinique. 105 IRM obtenues à V1 (n=43), V2 (n=33) and V3 (n=29). Augmentation significative et bilatérale des volumes hippocampiques observée dès V2. Diminution de la GFA bilatéralement entre V1-V2. Diminution unilatérale gauche de la DM et bilatérale de la DA entre V1-V3. Augmentation unilatérale droite du NDI entre V1-V3, diminution de la Fiso bilatéralement entre V1-V2, augmentation bilatérale de l'ODI dès V2. Pas de corrélation avec la sévérité initiale ou la réponse clinique post-ECT. Après ECT, l'analyse des paramètres anatomiques et de diffusion hippocampique en IRM montre une augmentation bilatérale du volume, une diminution des GFA, DA et Fiso, une augmentation des NDI et ODI, compatibles avec une accélération de la neurogénèse hippocampique.

IntroductionFolates, the main actors in one-carbon (C1) metabolism, are involved in synthesising monoamines and maintaining genomic stability. Previous studies support the association between C1 metabolism and schizophrenia. The main purpose of this study was to assess the prevalence of plasma folate, and/or vitamin B12 deficiencies and hyperhomocysteinemia in young patients with psychotic disorders.MethodsWe included young inpatients (15–30 years old) with psychosis between 2014 and 2017 from Sainte-Anne Hospital in Paris. Plasma folate, vitamin B12 deficiency and homocysteinemia dosages were done at admission. Clinical data were extracted retrospectively, and patients diagnosed with a first-episode psychosis (FEP), schizophrenia, schizoaffective disorder, or persistent delusional disorder were retained for the analysis.ResultsAmong the 334 inpatients, 188 (56%) had C1 dosages available (135 males; 53 females). From the 188 patients, 32% had a C1 abnormality. This abnormality reached 38% of FEP patients. The most frequent abnormality was folate deficiency: 21% of all patients and 27% of FEP. Lower levels of folates were found in males compared to females (p = 0.02) and were correlated with more severe disorder, as assessed by Clinical Global Impression – Severity (CGI-S; p = 0.009). Antipsychotic dosage was positively associated with B12 levels (p = 0.013) and negatively with homocysteinemia (p = 0.034).ConclusionOne-carbon metabolism anomalies in young patients with psychotic disorders are highly prevalent, reaching almost half of the patients with FEP. Potential protective effects from females and antipsychotics have emerged. These results spotlight the need for new therapeutic prospects, such as folate supplementation, to achieve personalised medical approaches to the early stages of psychotic disorders.