Diffusion Kurtosis Imaging and High-Resolution MRI Demonstrate Structural Aberrations of Caudate Putamen and Amygdala after Chronic Mild Stress

Rafael Delgado Y Palacios,Marleen Verhoye,Kim Henningsen,Ove Wiborg,Annemie Van Der Linden,Huafu Chen

doi:10.1371/journal.pone.0095077

Rafael Delgado Y Palacios, Marleen Verhoye + Show 4 more

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https://doi.org/10.1371/journal.pone.0095077

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Journal: PloS one	Publication Date: Apr 16, 2014
Citations: 56	License type: CC BY 4.0

Affiliation: University of Antwerp, Aarhus University Hospital

Abstract

The pathophysiology of major depressive disorder (MDD) and other stress related disorders has been associated with aberrations in the hippocampus and the frontal brain areas. More recently, other brain regions, such as the caudate nucleus, the putamen and the amygdala have also been suggested to play a role in the development of mood disorders. By exposing rats to a variety of stressors over a period of eight weeks, different phenotypes, i.e. stress susceptible (anhedonic-like) and stress resilient animals, can be discriminated based on the sucrose consumption test. The anhedonic-like animals are a well validated model for MDD. Previously, we reported that in vivo diffusion kurtosis imaging (DKI) of the hippocampus shows altered diffusion properties in chronically stressed rats independent of the hedonic state and that the shape of the right hippocampus is differing among the three groups, including unchallenged controls. In this study we evaluated diffusion properties in the prefrontal cortex, caudate putamen (CPu) and amygdala of anhedonic-like and resilient phenotypes and found that mean kurtosis in the CPu was significantly different between the anhedonic-like and resilient animals. In addition, axial diffusion and radial diffusion were increased in the stressed animal groups in the CPu and the amygdala, respectively. Furthermore, we found that the CPu/brain volume ratio was increased significantly in anhedonic-like animals as compared with control animals. Concurrently, our results indicate that the effects of chronic stress on the brain are not lateralized in these regions. These findings confirm the involvement of the CPu and the amygdala in stress related disorders and MDD. Additionally, we also show that DKI is a potentially important tool to promote the objective assessment of psychiatric disorders.

Highlights

Major depressive disorder (MDD) is a devastating disease with high prevalence and mortality
By demonstrating that mean kurtosis (MK) is the only diffusion metric that depicts the alterations of the microstructural anatomy that can be found in the hippocampus of stress exposed animals, we showed that the diffusion kurtosis metrics complements the conventional diffusion tensor metrics
Diffusion properties of the examined regions of interests (ROI) Analysis of the Diffusion kurtosis imaging (DKI) parameters showed that the caudate putamen (CPu) (Figure 3) and the amygdala (Figure 4) have different diffusion properties after chronic mild stress (CMS) exposure

Summary

Introduction

Major depressive disorder (MDD) is a devastating disease with high prevalence and mortality. It imposes severe suffering and puts a significant burden on our society as it affects all ages and socioeconomic classes. [7,8] animal studies reported changes of neuron morphology such as altered arborization, spinogenesis, etc., in these brain regions and in the amygdala, confirming the hypothesis of the involvement of multiple brain structures in the pathogenesis of depression. [13] DKI has been applied in several studies in both humans and animals, including pathological and normal conditions, such as ageing, Parkinson’s disease, attention-deficit hyperactivity disorder, etc. The estimated diffusion kurtosis measure is dimensionless and quantifies the deviation of the water displacement profile from the Gaussian distribution and can be assumed to be a measure for microstructural complexity. [12] Since its first introduction by Jensen et al (2005), DKI has already shown great promise in the characterization of microstructural anatomy of neuronal tissue. [13] DKI has been applied in several studies in both humans and animals, including pathological and normal conditions, such as ageing, Parkinson’s disease, attention-deficit hyperactivity disorder, etc. and has been reported to be more sensitive than conventional diffusion tensor imaging (DTI) for white and gray matter alterations. [12,14,15,16,17]

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