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T1-14
COMT AND ANKK1 GENETICS INTERACT WITH DE-
PRESSION TO INFLUENCE BEHAVIOR FOLLOWING
MODERATE/SEVERE TBI
John Myrga
1
, Shannon Juengst
1
, Michelle Failla
1,2
, Gary Galang
1
,
Yvette Conley
3–5
, Patricia Arenth
1
, Amy Wagner
1–3
1
Univ Pittsburgh, PhysicalMed/Rehab, Pittsburgh, USA
2
Univ Pittsburgh, Neuroscience, Pittsburgh, USA
3
Univ Pittsburgh, SafarCenter, Pittsburgh, USA
4
Univ Pittsburgh, HumanGenetics, Pittsburgh, USA
5
Univ Pittsburgh, HealthPromotion/Development, Pittsburgh, USA
Polymorphisms in the dopamine system, specifically the functional
polymorphism Val158Met in the catechol-o-methyl transferase
(COMT) gene and the Taq1A polymorphism in the ankyrin repeat and
kinase domain containing 1 (ANKK1) gene, are associated with
problematic behavior (e.g. impulsivity, aggression) in healthy popu-
lations. Additionally, stressful environments can interact with DA
genetics to influence behavior. To determine whether depression, a
condition associated with stress, interacts with polymorphisms to
adversely influence behavior following TBI, we assessed behavior and
depression status with the Frontal Systems Behavioral Scale (FrSBe)
and the Patient Health Questionnaire (PHQ-9) at 6&12 months in a
population of 97 Caucasian individuals with TBI. The FrSBe assesses
behaviors associated with frontal lobe dysfunction and produces
t-scores based on age, sex, and education adjusted norms. The PHQ9
is a validated assessment in the TBI population for depression. At 12-
months post-injury, we found a significant interaction between de-
pression and both Taq1A (p
=
0.003) and Val158Met (p
=
0.030) poly-
morphisms with regard to FrSBe scores. Depressed A2-homozygotes
scored
*
20 points worse than depressed A1-carrier counterparts
(p
=
0.053), and depressed Met-homozygotes scored
*
23 points
worse than depressed Val-carriers (p
=
0.064). Those without depres-
sion did not differ in behavior by Taq1A status (p
=
0.651) or
Val158Met status (p
=
0.464). A significant gene*depression interac-
tion (p
=
0.002) was also found at 12-months when assessing con-
current effects of Taq1A and Val158Met status on behavior.
Depressed individuals who were A2/A2 and Met-homozygotes re-
ported worse behavior than A2/A2 OR Met -homozygotes (p
=
0.003)
and those with no risk alleles (p
=
0.023). Significant interactions were
also noted on Apathy (p
=
0.006), Executive Function (p
=
0.002), and
Disinhibition (p
=
0.045) subscales. Similar, but non-significant, trends
were observed at 6-months. DA genetics may inform biosusceptibility
to behavioral problems following TBI and may help identify ‘‘at-risk’’
individuals with the greatest need for behavioral intervention.
Keywords: Rehabilomics, genes, behavior
T1-15
DELAYED AND ABBREVIATED ENVIRONMENTAL EN-
RICHMENT AFTER EXPERIMENTAL TRAUMATIC BRAIN
INJURY INCREASES HIPPOCAMPAL NEUROGENESIS
Naima Lajud Avila
1,2
, Jeffrey P. Cheng
1
, Corina O. Bondi
1
, Anthony
E. Kline
1
1
University of Pittsburgh, Physical Medicine & Rehabilitation and
Safar Center for Resuscitation Research, Pittsburgh, USA
2
Instituto Mexicano del Seguro Social, Divisio´n de Neurociencias,
Morelia, MX
Continuous environmental enrichment (EE) exposure improves neu-
robehavioral outcome after experimental traumatic brain injury (TBI).
One likely mechanism for the benefit is increased neurogenesis. De-
layed and abbreviated EE, which is more akin to clinical rehabilitation
in terms of timing, also enhances neurobehavioral recovery compa-
rably to early and continuous exposure after TBI; however, its effect
on hippocampal neurogenesis is unknown. Therefore,
the aim of this
study was to test the hypothesis that delayed and abbreviated EE is
sufficiently robust to induce hippocampal neuroplasticity after TBI
.
Anesthetized adult male rats received a controlled cortical impact
(2.8 mm depth at 4 m/sec) and were randomly assigned to either
standard housing (TBI
+
STD), continuous EE (TBI
+
EE), or delayed
and abbreviated EE (TBI
+
EE, 3 day delay, 6 hr day). BrdU (500 mg/
kg) was provided twice per day for 3 days and then sacrificed 10 days
later. The brains were cut on a freezing microtome at 40
l
m and
immunostaining for BrdU or triple immunofluorescence for BrdU,
DCX and NeuN was performed. Continuous EE lead to a 91%
(
p
£
0.05) increase in BrdU labeled nuclei density in the subgranular
zone of the dentate gyrus when compared to STD. Abbreviated EE
resulted in a 156% increase (
p
£
0.01) relative to STD. Triple im-
munofluorescence showed there were no differences in the percentage
of BrdU/DCX or BrdU/NeuN double labeled cells among the groups;
however in the continuous EE group, DCX positive cells displayed
larger ramifications when compared to abbreviated EE. In conclusion,
abbreviated EE with a 3 day delay effectively induced hippocampal
neurogenesis after TBI, which supports the hypothesis. These findings
elucidate a possible mechanism for the benefits observed with both
continuous and delayed-and-abbreviated EE.
Keywords: controlled cortical impact, environmental enrichment,
neurogenesis, immunostaining
T1-16
DEPRESSIVE SYMPTOMS ALTER AMYGDALA CON-
NECTIVITY IN TRAUMATIC BRAIN INJURY
Kihwan Han
1
, Sandra Chapman
1
, Daniel Krawczyk
1,2
1
University of Texas at Dallas, Center for BrainHealth, School of
Behavioral and Brain Sciences, Dallas, USA
2
University of Texas Southwestern Medical Center, Department of
Psychiatry, Dallas, USA
Depression is one of the most common psychiatric conditions in
chronic Traumatic Brain Injury (TBI). While depression has detri-
mental effects on chronic TBI individuals, there have been few in-
vestigations of neuroimaging biomarkers for comorbid depression in
TBI. Here, we utilized resting-state functional Magnetic Resonance
Imaging to identify altered amygdala connectivity in individuals with
chronic TBI who exhibited comorbid depressive symptoms (N
=
30),
relative to chronic TBI individuals having minimal depressive
symptoms (N
=
24). Connectivity analysis of these TBI sub-groups
revealed that the TBI
+
depressive symptoms group showed relatively
increased left amygdala connectivity with the bilateral precuneus,
dorsal and medial superior frontal gyri and paracentral lobules; the left
postcentral gyrus; the right insula, lingual gyrus, anterior prefrontal
gyrus and precentral gyrus (
p
cluster
<
0.05,
p
voxel
<
0.005). The
TBI
+
depressive symptoms group also exhibited relatively increased
right amygdala connectivity with the bilateral middle cingulate cor-
tices, insulae, dorsal and medial superior frontal gyri, paracentral
lobules, pre- and postcentral gyri, dorsolateral prefrontal gyri and
lingual gyri; left inferior frontal gyrus, dorsal anterior cingulate cor-
tex, anterior fusiform gyrus and anterior cerebellar vermis; right
thalamus and caudate head as well as relatively reduced right amyg-
dala connectivity with the left caudate body and the right caudate tail.
We conducted a post-hoc analysis on selected regions of interest
analysis that showed group differences in amygdala connectivity
A-7