Dataset Information

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 (BP_ND) [¹¹C]PHNO values were used to index D2/D3 receptor availability, and were calculated using a reference region procedure. Differences in BP_ND were examined using voxelwise and region-of-interest analyses. White matter microstructure integrity, quantified by fractional anisotropy (FA), was assessed and correlated with BP_ND.

Results

Lower [¹¹C]PHNO BP_ND was found in the caudate across all TBI patients when compared to controls. Lower [¹¹C]PHNO BP_ND was observed in the caudate of TBI-MDD patients and increased [¹¹C]PHNO BP_ND in the Amygdala of TBI-NON patients compared to controls. There were no significant differences in [¹¹C]PHNO BP_ND 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 BP_ND correlated with FA within the nigro-caudate tract.

Conclusions

[¹¹C]PHNO BP_ND is abnormal following TBI, which indicates post-traumatic changes in D2/D3 receptors. Patterns of [¹¹C]PHNO BP_ND 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.

SUBMITTER: Jolly AE

PROVIDER: S-EPMC6664227 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Jolly Amy E AE Raymont Vanessa V Cole James H JH Whittington Alex A Scott Gregory G De Simoni Sara S Searle Graham G Gunn Roger N RN Sharp David J DJ

NeuroImage. Clinical 20190722

<h4>Objective</h4>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.<h4>Methods</h4>Twelve moderate-severe TBI patients and 26 controls were imaged using [<sup>11</sup>C]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 (D ...[more]

PMID: 31352218

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Project description:The underlying pathophysiology of paediatric mild traumatic brain injury and the time-course for biological recovery remains widely debated, with clinical care principally informed by subjective self-report. Similarly, clinical evidence indicates that adolescence is a risk factor for prolonged recovery, but the impact of age-at-injury on biomarkers has not been determined in large, homogeneous samples. The current study collected diffusion MRI data in consecutively recruited patients (n = 203; 8-18 years old) and age and sex-matched healthy controls (n = 170) in a prospective cohort design. Patients were evaluated subacutely (1-11 days post-injury) as well as at 4 months post-injury (early chronic phase). Healthy participants were evaluated at similar times to control for neurodevelopment and practice effects. Clinical findings indicated persistent symptoms at 4 months for a significant minority of patients (22%), along with residual executive dysfunction and verbal memory deficits. Results indicated increased fractional anisotropy and reduced mean diffusivity for patients, with abnormalities persisting up to 4 months post-injury. Multicompartmental geometric models indicated that estimates of intracellular volume fractions were increased in patients, whereas estimates of free water fractions were decreased. Critically, unique areas of white matter pathology (increased free water fractions or increased neurite dispersion) were observed when standard assumptions regarding parallel diffusivity were altered in multicompartmental models to be more biologically plausible. Cross-validation analyses indicated that some diffusion findings were more reproducible when ∼70% of the total sample (142 patients, 119 controls) were used in analyses, highlighting the need for large-sample sizes to detect abnormalities. Supervised machine learning approaches (random forests) indicated that diffusion abnormalities increased overall diagnostic accuracy (patients versus controls) by ∼10% after controlling for current clinical gold standards, with each diffusion metric accounting for only a few unique percentage points. In summary, current results suggest that novel multicompartmental models are more sensitive to paediatric mild traumatic brain injury pathology, and that this sensitivity is increased when using parameters that more accurately reflect diffusion in healthy tissue. Results also indicate that diffusion data may be insufficient to achieve a high degree of objective diagnostic accuracy in patients when used in isolation, which is to be expected given known heterogeneities in pathophysiology, mechanism of injury and even criteria for diagnoses. Finally, current results indicate ongoing clinical and physiological recovery at 4 months post-injury.

Dataset Information

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

Objective

Methods

Results

Conclusions

Publications

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

Similar Datasets

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