Cerebellar White Matter Integrity and Depression in Chronic TBI

Deborah M. Little PhDPatrick Glang

Michelle Pennington BABaylor Scott & White Health

University of OregonTexas A&M Health Sciences

College of Medicine

Funding and DisclosureThere are no financial conflicts of interest related to

the specific topic of this lecture.

Funding - TBIDepartment of Defense W81XWH-08-1-0732 (Little)Veterans Administration RR&D 1I01RX000394

(Little)Veterans Administration RR&D 1I01RX000304

(Morissette)

Scope of the ProblemPopulation based retrospective, self report studies have repeatedly found and reported an increased risk of MDD in persons who also report a history of TBI. However, these studies lack many controls needed to assess the true prevalence and incidence of these comorbid conditions and do not address the primary question as to whether TBI results in increased risk of MDD. TBI traumatic brain injury (mild, moderate, severe/traumatic)

Known: 1. Holsinger and colleagues found an increased lifetime prevalence of MDD in

veterans (~18%; WWII) than in combat controls (~14%)2. Surveillance (Jorge et al 1993; Seel et al 2003; Kreutzer et al 2001), Jorge

et al, 2004) studies show an increased rate of dx of MDD in those with a recent history of TBI • Case control studies, Hospital based recruitment• Patient history of premorbid depression, anxiety disorders increased

risk of depression post-TB3. Depressive symptoms in Chronic TBI have been shown to have

neuroanatomical correlates that include those in the fronto cerebellar circuit.

Why look at the cerebellum?- Preliminary data from our lab using voxel based

morphometric analyses identified the cerebellum as the region most related to current depressive symptoms

Why look at the cerebellum?- Preliminary data in combat-related TBI has shown

that white matter injury in the cerebellum may be more specific and sensitive to depressive symptoms when compared to PTSD

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Why look at the cerebellum?- Biomechanical modelling highlights sensitivity of the

cerebellum as a position structure of high vulnerability to shear and strain injury

- The cerebellum has been demonstrated to be related to MDD in non-TBI pediatric and adult patients including localized ischemic insult

- Cognitive Cerebellar Affective Syndrome, Schmahmann 1998

Methods A total of 24 patients with a history of

non-combat, single, closed-head type TBI (24mild, 24mod) and 24 demographically matched controls participated

For the TBI patients, the index injury was required to have occurred after age 17 and at least 12 months prior to the study. All subjects were required to be native speakers of English.

Detailed neuropsychological testing was also performed to characterize executive function, memory, and attention.

Methods Imaging was conducted using parallel

imaging together with an 16-channel phased-array head coil

Fractional anisotropy (FA) was extracted from regions of interest in the pontine cross tracts, middle and superior cerebellar peduncles, portions of the cortico-spinal tract and medial lemniscus (bilaterally when appropriate).

Three regions of interest were placed on each tract. Regions were drawn independently by two raters (PG, MP) and exceeded reliability of 0.91

Results

Inf CSTMedial lemniscus Pontine crossing tracts

• The moderate to severe TBI group had reduced FA – relative to controls – in all ROIs

• The moderate to severe TBI group differed from the mild TBI group in all ROIs

• The mild TBI differed from controls for regions of interest in the medial lemniscus, pontine crossing tracts and inferior portions of the CST (p<0.01 for all)

ResultsCorrelations between cerebellar FA and BDI II• No significant correlations between FA and BDI

on any measures for controls

• For the mild TBI, BDI II total score was associated with reduced FA in the medial lemniscus (p=0.006)

• For moderate to severe, depressive symptoms were associated with reduced FA in the pontine fibers (p=0.04), cortico-spinal tract (p=0.02) and superior cerebellar peduncles (p=0.04)

ConclusionsDamage to the cerebellar white matter appears to have a relationship with depressive symptoms in chronic TBIThose tracts that cross or traverse from the spine up through superior cortical areas appear to be more affected by non-combat acceleration-deceleration injury

Preliminary investigations into volumetric alterations also appear to be altered in mild and moderate TBI which is not consistent with other studies of mild TBI

FA of the caudate and SN also show similar relationships raising the question of the role of the dopaminergic network in TBI

Finally, cerebellar integrity appears to account for depressive symptoms along the same magnitude as gross measures of cortical white matter integrity.

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Acknowledgements

•Deborah M. Little PhD•Ulrich Mayr PhD•Michelle Pennington BA• Jane Gillett •University of Oregon•Baylor University • Scott & White Healthcare