Marie Chupin

Can voxel based morphometry, manual segmentation and automated segmentation equally detect hippocampal volume differences in acute depression?

CONTEXT According to meta-analyses, depression is associated with a smaller hippocampus. Most magnetic resonance imaging (MRI) studies among middle aged acute depressed patients are based on manual segmentation of the hippocampus. Few studies used automated methods such as voxel-based morphometry (VBM) or automated segmentation that can overcome certain drawbacks of manual segmentation (essentially intra- and inter-rater variability and operator time consumption). OBJECTIVE The aim of our study was to compare the sensitivity of manual segmentation, automated segmentation and VBM to detect hippocampal structural changes in middle aged acute depressed population. METHOD Twenty-one middle aged depressed inpatients and 21 matched controls were compared regarding their hippocampal structure using VBM with SPM5, manual segmentation and an automated segmentation algorithm. The VBM-ROI analysis was performed using two different normalization methods: the standard approach implemented in SPM5 and the most recent DARTEL algorithm. RESULTS Using VBM-DARTEL, when corrected for multiple comparisons, significant volume differences were detected between groups in different regions and more specifically in hippocampus with ROI analyses. Whereas using standard VBM (without DARTEL), ROI analyses did not show bilateral volume between group differences. Significant hippocampal volume reductions between patients and controls were also detected using manual segmentation (-11.6% volume reduction, p<0.05) and automated segmentation (-9.7% volume reduction, p<0.05). VBM-DARTEL and automated segmentation show equal sensitivity in detecting hippocampal differences in depressed patients, while standard VBM was unable to detect hippocampal changes. Both VBM-DARTEL and automated segmentation could be used to perform large scale volumetric studies in humans. The new automated segmentation technique could further explore and detect hippocampal subpart differences that could be very useful for clarifying physiopathology of psychiatric disorders.

Brain volumes and Val66Met polymorphism of the BDNF gene: local or global effects?

A common Single-Nucleotide Polymorphism in the Brain-Derived Neurotrophic Factor (BDNF) gene coding the Val66Met substitution in the pro-BDNF protein has been associated with a number of behavioural and neuroanatomical phenotypes; the latter include, for example, regional differences in volumes of the hippocampus and prefrontal grey matter. Here, we show that the observed regional differences may not stem from a localised effect of this gene. Our analysis of regional brain volume in a cohort of 331 adolescents indicates that the Val66Met substitution has a global effect on brain volume, and that the observed local differences are to be expected if brain allometry—the covariance pattern of regional brain volumes—is taken into account.

P2a-4 Etude Hippocampe : Evaluation de l’efficacité du donépézil versus placebo sur des marqueurs IRM et cliniques chez des patients présentant des troubles cognitifs légers

Introduction Le donepezil a montre, dans de nombreuses etudes, une efficacite symptomatique chez des patients atteints de maladie d’Alzheimer (MA), notamment chez les patients au stade leger. Le donepezil pourrait aussi contribuer a ralentir l’evolution vers la maladie, a des stades tres precoces de la MA. Pour tester cette hypothese, l’objectif de notre etude est d’evaluer, dans un essai controle vs placebo, l’impact du donepezil 10 mg/jour sur l’evolution du volume hippocampique,considere comme un bon marqueur de la progression de la maladie, chez des sujets ayant des troubles cognitifs legers de type amnesique. Materiel/Methode L’etude “Hippocampe” est une etude francaise multicentrique en double aveugle, randomisee versus placebo, avec deux groupes paralleles, d’une duree de 52 semaines. Les patients inclus repondent aux criteres suivants : (1) syndrome amnesique de type temporal interne mesure par le test “Free and Cued Selective Reminding” (rappel libre≤17 ou rappel total ere IRM est effectuee avant la visite de randomisation, validee par un centre de lecture centralise. Une 2 nde IRM est realisee a la visite finale (52 semaines) ou, en cas de sortie prematuree, apres 6 mois. Le Volume Hippocampique est mesure par une technique de segmentation semi automatique. Resultats Au 1 er mai 2009, 170 patients ont ete randomises dans 24 centres. L’inclusion se terminera le 30 juin 2009. Des analyses preliminaires montrent qu’environ 10% des patients quittent l’etude avant la 2e IRM. Ils ne different pas des patients poursuivant l’essai pour l’âge, le sexe (p=0.39) ou le volume hippocampique a l’inclusion (p=0.23). Les principales raisons pour une sortie prematuree d’essai sont la survenue d’un evenement indesirable (41.6%) et la conversion vers une MA avant la fin de l’essai (16.7%). Ces resultats seront completes et mis a jour. Nous presenterons egalement une description detaillee de l’echantillon final pour les caracteristiques cliniques et radiologiques a l’entree dans l’etude. Conclusion Cette etude va permettre d’evaluer l’impact du donepezil sur les marqueurs IRM a des stades precoces de la MA.

Erratum to: Brain volumes and Val66Met polymorphism of the BDNF gene: local or global effects?

Erratum to: Brain Struct Funct (2009) 213:501–509DOI 10.1007/s00429-009-0203-yIn the original published version of this article the categorywas not given correct.The category should be Original Article (not HumanBrain: Structure, Function & Behavior).Furthermore, there are errors in pages three and five. Onthe third page, the correct formula should read:M