Higher in vivo Cortical Intracellular Volume Fraction Associated with Lithium Therapy in Bipolar Disorder: A Multicenter NODDI Study

Samuel Sarrazin 1, 2, 3, * Cyril Poupon 2 Achille Teillac 2 Jean-François Mangin 2 Mircea Polosan 4 Pauline Favre 2, 3 Charles Laidi 2, 1, 5, 3 Marc-Antoine d'Albis 1, 2, 5, 3 Marion Leboyer 1, 5, 3 Pierre-Marie Lledo 6 Chantal Henry 6 Josselin Houenou 3, 2, 5, 1, *
* Corresponding author
3 U955 Inserm - IMRB - UPEC UP12 - Team 15, "Translational Psychiatry"
IMRB - Institut Mondor de Recherche Biomédicale
4 Equipe 11 : Fonctions cérébrales et neuromodulation
UJF - Université Joseph Fourier - Grenoble 1, CEA - Commissariat à l'énergie atomique et aux énergies alternatives, INSERM - Institut National de la Santé et de la Recherche Médicale : U836, [GIN] Grenoble Institut des Neurosciences
Abstract : BACKGROUND: MRI studies in patients with bipolar disorder have suggested that lithium is associated with grey matter increases that may underlie its therapeutic effects. However, the relationship between grey matter volume and cellular microstructural changes is not straightforward, as modifications of different cellular compartments of grey matter may be involved. OBJECTIVES: Our aim was to test the hypothesis that dendritic density is higher in patients undergoing lithium therapy than in patients without lithium, using advanced modelling of water diffusion investigated with MRI. METHOD: We included 41 patients and 40 controls matched for age and gender from two sites. All subjects underwent 3T MRI with 3 shells of diffusion. We used neurite orientation dispersion and density imaging to compare the grey matter neurite density between patients undergoing lithium therapy or not and control subjects. RESULTS: We found a significant group effect in the left prefrontal region (p = 0.001, Bonferroni corrected): patients without lithium had a lower frontal neurite density than controls (p = 0.009), while those on lithium had a higher mean neurite density than those without (p < 0.001). Patients on lithium were not different from controls (p = 0.08). CONCLUSIONS: This is the first study to report in vivo evidence of preserved neurite density of the prefrontal cortex in humans associated with lithium intake. Changes of intracellular volume fraction are thought to reflect changes of grey matter microstructural organization. This reinforces the hypothesis of lithium having a positive effect on the neuronal compartment in humans.
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https://www.hal.inserm.fr/inserm-02098022
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Submitted on : Friday, April 12, 2019 - 12:06:55 PM
Last modification on : Friday, October 4, 2019 - 1:07:04 AM

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Samuel Sarrazin, Cyril Poupon, Achille Teillac, Jean-François Mangin, Mircea Polosan, et al.. Higher in vivo Cortical Intracellular Volume Fraction Associated with Lithium Therapy in Bipolar Disorder: A Multicenter NODDI Study. Psychotherapy and Psychosomatics, Karger, 2019, Epub ahead of print. ⟨10.1159/000498854⟩. ⟨inserm-02098022⟩

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