Dopamine D2/D3 receptor abnormalities after traumatic brain injury and their relationship to post-traumatic depression.

Amy E Jolly,Gregory Scott,Roger N Gunn,Graham Searle,David J Sharp,Vanessa Raymont,Alex Whittington,James H Cole,Sara De Simoni

doi:10.1016/j.nicl.2019.101950

Abstract

ObjectiveTo investigate dopamine D2/D3 receptor availability following traumatic brain injury (TBI) and their relationship to the presence of DSM-IV Major Depressive Disorder (MDD) and patterns of axonal injury.MethodsTwelve moderate-severe TBI patients and 26 controls were imaged using [11C]PHNO positron emission tomography (PET) and structural magnetic resonance imaging (MRI). TBI patients and a second group of 32 controls also underwent diffusion tensor imaging (DTI) and neuropsychological assessment. Patients included six with post-injury MDD (TBI-MDD) and six without (TBI-NON). Non-displaceable binding potential (BPND) [11C]PHNO values were used to index D2/D3 receptor availability, and were calculated using a reference region procedure. Differences in BPND were examined using voxelwise and region-of-interest analyses. White matter microstructure integrity, quantified by fractional anisotropy (FA), was assessed and correlated with BPND.ResultsLower [11C]PHNO BPND was found in the caudate across all TBI patients when compared to controls. Lower [11C]PHNO BPND was observed in the caudate of TBI-MDD patients and increased [11C]PHNO BPND in the Amygdala of TBI-NON patients compared to controls. There were no significant differences in [11C]PHNO BPND between TBI-MDD and TBI-NON patients. Furthermore, DTI provided evidence of axonal injury following TBI. The uncinate fasciculus and cingulum had abnormally low FA, with the uncinate particularly affected in TBI-MDD patients. Caudate [11C]PHNO BPND correlated with FA within the nigro-caudate tract.Conclusions[11C]PHNO BPND is abnormal following TBI, which indicates post-traumatic changes in D2/D3 receptors. Patterns of [11C]PHNO BPND seen in patients with and without MDD suggest that further research would be beneficial to determine whether the use of dopaminergic treatment might be effective in the treatment of post-traumatic depression.

Highlights

Traumatic brain injury (TBI) often leads to cognitive and psychiatric problems (Whitnall et al, 2006; Fleminger and Ponsford, 2005)
We investigated whether reductions to dopaminergic nuclei volume were present in patients and whether this related to reduced [11C]PHNO BPND in the caudate of TBI patients
We investigated whether TBI patients with Major Depressive Disorder (MDD) have greater evidence of axonal injury compared to TBI-NON patients and controls

Summary

Introduction

Traumatic brain injury (TBI) often leads to cognitive and psychiatric problems (Whitnall et al, 2006; Fleminger and Ponsford, 2005). These are associated with dopaminergic abnormalities, including direct damage to dopaminergic nuclei, axonal injury to dopaminergic neurons and subsequent changes in dopamine production, metabolism and clearance (Jenkins et al, 2016; Bales et al, 2009). Neuroimaging studies of the human dopaminergic system after TBI have been limited. Changes in dopaminergic function may be relevant to post-traumatic depression, which is very common (Jorge et al, 1993).

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