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Psychother Psychosom. 2019 Apr 5:1-6. doi: 10.1159/000498854. [Epub ahead of print]

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

Sarrazin S1,2,3,4, Poupon C3, Teillac A3, Mangin JF3, Polosan M5, Favre P1,3, Laidi C1,2,3,4,6, D Apos Albis MA1,2,3,6, Leboyer M1,2,4,6, Lledo PM7, Henry C7, Houenou J8,9,10,11,12.

Author information

1
INSERM U955, IMRB, Team 15, "Translational Psychiatry", Créteil, France.
2
Assistance Publique - Hôpitaux de Paris, DHU PePSY, Department of Psychiatry, Mondor University Hospitals, Créteil, France.
3
NeuroSpin, Atomic Energy Commission, Gif-sur-Yvette, France.
4
Université Paris Est Créteil, Créteil, France.
5
Grenoble Institut des Neurosciences (GIN), INSERM U836, La Tronche, France.
6
Fondation FondaMental, Créteil, France.
7
Unité Perception et Mémoire, Institut Pasteur, Paris, France.
8
INSERM U955, IMRB, Team 15, "Translational Psychiatry", Créteil, France, josselin.houenou@inserm.fr.
9
Assistance Publique - Hôpitaux de Paris, DHU PePSY, Department of Psychiatry, Mondor University Hospitals, Créteil, France, josselin.houenou@inserm.fr.
10
NeuroSpin, Atomic Energy Commission, Gif-sur-Yvette, France, josselin.houenou@inserm.fr.
11
Université Paris Est Créteil, Créteil, France, josselin.houenou@inserm.fr.
12
Fondation FondaMental, Créteil, France, josselin.houenou@inserm.fr.

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.

KEYWORDS:

Bipolar disorder; Grey matter increase; Lithium therapy; Neurite density

PMID:
30955011
DOI:
10.1159/000498854

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