Precision-medicine findings from the FACE-SZ cohort to develop motivation-enhancing programs in real-world schizophrenia

Background: In people with schizophrenia, major areas of everyday life are impaired, including independent living, productive activities, social relationships and overall quality of life. Enhanced understanding of factors that hinder real-life functioning is vital for treatments to translate into more positive outcomes. Aim: The goal of the present study was to identify factors associated with motivation deficits in real-life schizophrenia, and to assess its contribution to impaired functioning and quality of life. Methods: Based on previous literature and clinical experience, several factors were selected and grouped into factors potentially explaining motivation deficits. Some of these variables were never investigated before in relationship with motivation deficits. Results: In 561 patients with schizophrenia of the national FACE-SZ cohort living in the community, 235 (41.9%) reported severe motivation deficits. These deficits were found to be significantly associated with impaired socially useful activities, psychological and physical quality of life (in almost all domains), alcohol use disorder (aOR = 2.141, p = 0.021), severe nicotine dependence (aOR = 2.906, p < 0.001) independently of age and sex. No significant association was found for body mass index, metabolic syndrome or physical activity level. In the second model, we identified the following modifiable factors associated with motivation deficits: history of suicide attempt (aOR = 2.297, p = 0.001), positive symptoms (aOR = 1.052, p = 0.006), current major depressive episode (aOR = 2.627, p < 0.001), sleep disorders (aOR = 1.474, p = 0.024) and lower medication adherence (aOR = 0.836, p = 0.001) independently of gender, current alcohol use disorder, second-generation antipsychotics and akathisia. No significant association was found for negative symptoms, childhood trauma and inflammation. These results were maintained after removing patients with schizoaffective disorders or those with major depressive disorder. Interpretation: Motivation deficits are frequent and remain persistent unmet need in real-world schizophrenia that should be addressed in future guidelines. Based on our results, literature and clinical experience, we recommend to address in priority major depression, sleep, suicide, positive symptoms (when present and as early as possible) and medication adherence to improve motivation deficits of schizophrenia. © 2022 Informa UK Limited, trading as Taylor & Francis Group.Sorbonne Universités à Paris pour l'Enseignement et la RechercheFondaMental-Cohorte

L'efficacité de la stimulation magnétique transcrânienne profonde dans le traitement de la dépression pharmaco-résistante : une étude clinique comparative couplée à la TEP cérébrale au 18FDG

Introduction : la stimulation magnétique transcrânienne répétitive (rTMS) peut être proposée dans la dépression résistante. Elle consiste en une stimulation cérébrale non invasive par une bobine délivrant des impulsions magnétiques sur le crâne. Ciblée sur le cortex préfrontal dorsolatéral (dlPFC) gauche, la rTMS est efficace dans 30-40 % des cas. Ces résultats pourraient être améliorés avec des bobines récentes dites profondes (« Hesed » et « Double-Cône ») présumées plus pénétrantes que les bobines standards (« figure-en-huit »). De plus, l’identification de marqueurs prédictifs de réponse à cette technique permettrait de mieux sélectionner les patients. L’objectif principal de ce travail est l’évaluation de l’efficacité de la rTMS profonde dans la dépression résistante. L’objectif secondaire est la recherche de marqueurs métaboliques de réponse à la rTMS. Méthode : nous avons réalisé une étude monocentrique, comparative, randomisée, en double aveugle, en deux bras : rTMS profonde (bobine Double Cône) et rTMS standard (bobine figure-en-huit). Les sujets bénéficiaient de vingt séances de rTMS appliquées sur le dlPFC gauche et d’une imagerie TEP-18FDG cérébrale pré et post cure. L’analyse principale était conduite en intention de traiter (ITT). Le critère de jugement (CJ) principal pour évaluer l’efficacité clinique était le score MADRS et les CJ secondaires étaient les scores QIDS-SR-16 et SF-12. Le métabolisme cérébral était comparé par une cartographie statistique paramétrique complétée d’analyses de corrélations avec les CJ précédemment citées.Résultats : de mars 2015 à octobre 2018, 45 sujets étaient randomisés entre rTMS standard (23 patients) et rTMS profonde (22 patients). Trente-six patients réalisaient l’intégralité du protocole. Les analyses comparatives en ITT ne montraient pas de différence significative sur les CJ. Le taux de réponse au score MADRS était de 44,4% dans le groupe rTMS standard et de 33,3% dans le groupe rTMS profonde (p=0,494). Le métabolisme glucidique du noyau caudé bilatéral avant stimulation était négativement corrélé aux scores MADRS (r=-0,418) et QIDS-SR-16 (r=-0,428), obtenus après la cure de rTMS.Conclusion : aucune différence d’efficacité clinique entre rTMS standard et profonde est mise en évidence. Un hypométabolisme pré-thérapeutique du noyau caudé suggèrerait une résistance à la rTMS. Cette hypothèse encourage la poursuite de l’étude des marqueurs métaboliques

Longitudinal Changes in Cognition, Behaviours, and Functional Abilities in the Three Main Variants of Primary Progressive Aphasia: A Literature Review

Primary progressive aphasias (PPAs) are a group of neurodegenerative diseases presenting with insidious and relentless language impairment. Three main PPA variants have been described: the non-fluent/agrammatic variant (nfvPPA), the semantic variant (svPPA), and the logopenic variant (lvPPA). At the time of diagnosis, patients and their families’ main question pertains to prognosis and evolution, but very few data exist to support clinicians’ claims. The objective of this study was to review the current literature on the longitudinal changes in cognition, behaviours, and functional abilities in the three main PPA variants. A comprehensive review was undertaken via a search on PUBMED and EMBASE. Two authors independently reviewed a total of 65 full-text records for eligibility. A total of 14 group studies and one meta-analysis were included. Among these, eight studies included all three PPA variants. Eight studies were prospective, and the follow-up duration was between one and five years. Overall, svPPA patients showed more behavioural disturbances both at baseline and over the course of the disease. Patients with lvPPA showed a worse cognitive decline, especially in episodic memory, and faster progression to dementia. Finally, patients with nfvPPA showed the most significant losses in language production and functional abilities. Data regarding the prodromal and last stages of PPA are still missing and studies with a longer follow-up observation period are needed

Brain PET metabolic substrate of TMS response in pharmaco-resistant depression

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Double cone coil rTMS efficacy for treatment-resistant depression: A prospective randomized controlled trial

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Brain SPECT perfusion and PET metabolism as discordant biomarkers in major depressive disorder

International audienceBrain SPECT perfusion and PET metabolism have been, most often interchangeably, proposed to study the underlying pathological process in major depressive disorder (MDD). The objective of this study was to specify similarities and inconsistencies between these two biomarkers according to global characteristics of the disease. We conducted a retrospective study in 16 patients suffering from treatment-resistant MDD who underwent, during the same current episode, a cerebral perfusion SPECT with 99m Tc-HMPAO and a metabolic PET with 18 F-FDG. Whole-brain voxel-based SPM(T) maps were generated in correlation with the number of depressive episodes and in correlation with the depression duration, separately for the two exams (p-voxel  20). Results No significant correlations were found between brain metabolism and either the number of depressive episodes or the duration of the disease, even at an uncorrected p-voxel < 0.005. On the other hand, the increased number of depressive episodes was correlated with decreased perfusion of the right middle frontal cortex, the right anterior cingulum cortex, the right insula, the right medial temporal cortex and the left precuneus. The increased depression duration was correlated with decreased perfusion of the right anterior cingulum cortex. Conclusions This preliminary study demonstrates more significant results with brain perfusion compared with glucose metabolism in treatment-resistant MDD, highlighting the value of brain SPECT despite less favourable instrumentation detection compared to PET