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

Abstract

Objective: To 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. Methods: Twelve 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. Results: Lower [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.