Chung YA, Kim SH, Chung SK, Chae JH, Yang DW, Sohn HS et al. Alterations in cerebral perfusion in posttraumatic stress disorder patients without re-exposure to accident-related stimuli. Clin Neurophysiol 117: 637-642

Article (PDF Available)inClinical Neurophysiology 117(3):637-42 · April 2006with55 Reads
DOI: 10.1016/j.clinph.2005.10.020 · Source: PubMed
Abstract
Functional neuroimaging studies have shown abnormalities of limbic regions in patients with posttraumatic stress disorder (PTSD) during symptom provocation and cognitive activation. The aim of this study was to determine whether PTSD patients without re-exposure to accident-related stimuli would exhibit alterations in cerebral perfusion compared with age-matched normal subjects. Brain perfusion SPECT was measured in medication-free 23 PTSD patients and 64 age-matched healthy subjects under resting conditions and analyzed using statistical parametric mapping to compare between the patient and control groups. We found that PTSD patients exhibited increased cerebral blood perfusion in limbic regions and decreased perfusion in the superior frontal gyrus and parietal and temporal regions in comparison with those of the normal controls. This result indicates that PTSD patients have alterations in cerebral perfusion of limbic regions and the frontal and temporal cortex without re-exposure to accident-related stimuli. This finding supports the hypothesis of the involvement of limbic regions, which might be associated with the regulation of emotion and memory, in the pathophysiology of PTSD.
Alterations in cerebral perfusion in posttraumatic stress
disorder patients without re-exposure to accident-related stimuli
Yong An Chung
a
, Sung Hoon Kim
a
, Soo Kyo Chung
a
, Jeong-Ho Chae
b
,
Dong Won Yang
c
, Hyung Sun Sohn
a
, Jaeseung Jeong
d,e,
*
a
Department of Radiology, The Catholic University of Korea, Seoul, South Korea
b
Department of Psychiatry, The Catholic University of Korea, Seoul, South Korea
c
Department of Neurology College of Medicine, The Catholic University of Korea, Seoul, South Korea
d
Department of BioSystems, Korea Advanced Institute of Science and Technology (KAIST), Yuseong-gu,
Kuseong-dong 373-1, Daejeon 305-701, South Korea
e
Department of Psychiatry, Columbia College of Physicians and Surgeons and the New York State Psychiatric Institute,
New York, NY 10032, USA
Accepted 12 October 2005
Available online 19 January 2006
Abstract
Functional neuroimaging studies have shown abnormalities of limbic regions in patients with posttraumatic stress disorder (PTSD) during
symptom provocation and cognitive activation.
Objective: The aim of this study was to determine whether PTSD patients without re-exposure to accident-related stimuli would exhibit
alterations in cerebral perfusion compared with age-matched normal subjects.
Methods: Brain perfusion SPECT was measured in medication-free 23 PTSD patients and 64 age-matched healthy subjects under resting
conditions and analyzed using statistical parametric mapping to compare between the patient and control groups.
Results: We found that PTSD patients exhibited increased cerebral blood perfusion in limbic regions and decreased perfusion in the superior
frontal gyrus and parietal and temporal regions in comparison with those of the normal controls.
Conclusions: This result indicates that PTSD patients have alterations in cerebral perfusion of limbic regions and the frontal and temporal
cortex without re-exposure to accident-related stimuli.
Significance: This finding supports the hypothesis of the involvement of limbic regions, which might be associated with the regulation of
emotion and memory, in the pathophysiology of PTSD.
q 2005 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.
Keywords: PTSD; SPECT; Accident-related stimuli; Limbic regions
1. Introduction
Posttraumatic stress disorder (PTSD) is an anxiety
disorder resulting from experiencing or witnessing an
extreme traumatic stressor that involved potential loss of
life or serious injury to the self or others. The symptoms of
PTSD are characterized by persistent re-experiencing of the
traumatic event, avoidance of stimuli associated with the
traumatic event, psychogenic amnesia, and increased
arousal. Furthermore, sleep disturbances, inappropriate
irritability, difficulty in concentration, and exaggerated
startle responses are often observed in PTSD patients
(Yehuda, 2002).
Neuroimaging studies using magnetic resonance
imaging (MRI), positron emission tomography (PET),
and single-photon emission tomography (SPECT) have
Clinical Neurophysiology 117 (2006) 637–642
www.elsevier.com/locate/clinph
1388-2457/$30.00 q 2005 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.
doi:10.1016/j.clinph.2005.10.020
*
Corresponding author. Address: Department of BioSystems, Korea
Advanced Institute of Science and Technology (KAIST), Yuseong-gu,
Kuseong-dong 373-1, Daejeon 305-701, South Korea. Tel.: C82 42 869
4319; fax: C82 42 869 4310.
E-mail address: jsjeong@kaist.ac.kr (J. Jeong).
provided valuable information on the pathophysiology
of PTSD (for reviews, see Bremner, 2002; Grossman
et al., 2002; H ull, 2002; Pitman et al., 2001).
Structural abnormalities in PTSD found with MRI
include reduced hippocampal volume (Bremner et al.,
1995; 1997; Gurvits et al., 1996; Stein et al., 1997)
and nonspecific white matter lesions (Canive et al.,
1997). These abnormalities might reflect pretrauma
vulnerability to developing PTSD, or they may be a
consequence of traumatic exposure, PTSD, and/or
PTSD sequelae (Pitman et al., 2001). Functional
neuroimaging stud ies on PTSD patients d uring symp-
tom provocation and cognitive activation have found
increased activation of the amygdala and anterior
paralimbic structures, which are kn own to regulate
negative emotions like fear (Rauch et al., 1996, 1997,
2000; Semple et al. , 2000; Shin e t al., 19 97a,b). In
addition, these studies have found failure of activation
of the cingulate cortex, which might play an inhibitory
role in response to trauma-related stimuli (Semple
et al., 1996; Shin et al., 1997b), and reduced activation
of Broca’s area (motor speech) and other nonlimbic
cortical regions (Rauc h et al., 1 996; Shin et al.,
1997a,b). These previous studies suggest that limbic
regions and the prefrontal and temporal cortex are
involved in pathogenesis of PTSD.
While previous functional neuroimaging studies on
PTSD patients have been mostly performed using symptom
provocation paradigms, there are few reports for eval uation
of the changes in regional cerebral blood flow (rCBF)
involved in PTSD without re-exposure to accident-related
stimuli. Sachinvala et al. (2000) studied 17 PTSD patients
under resting conditions using Tc-99m hexamethyl propy-
lene amine oxime SPECT to find an increase in cerebral
perfusion in the cingulate regions, the temporal and parietal
regions, the caudate/putamen region, and the orbital and
hippocampal regions in PTSD patients compared with the
control group. In addition, our group demonstrated, using
nonlinear dynamical analysis of the EEG, that PTSD
patients have globally reduced complexity of the electrical
brain activity under resting conditions compared with those
of the healthy subjects (Chae et al., 2004). These studies
suggest the possibility that PTSD patients may exhibit
alterations in cerebral perfusion without re-exposure to
accident-related stimuli.
Thus, in the present study, we investigated whether
PTSD patients would exhibit alterations in cer ebral
perfusion compared with normal subj ects without re-
exposure to accident-related stimuli. SPECT scanning of
PTSD patients and age-matched healthy subjects was
performed under resting conditions to examine alterations
in regional cerebral perfusion without provocative
stimuli. Given the significant role o f limbic and
paralimbic regions in the pathogenesis of PTSD, we
hypothesized that PTSD patients would sh ow a n
elevation of rCBF levels in these regions even without
provocation stimuli.
2. Materials and methods
2.1. Subjects
Regional CBF measurements of resti ng state using Tc-
99m ECD (ethyl cysteinate dimmer) S PECT were
performed on 23 patients with PTSD (M:FZ 13:10; ages,
21–63 years; mean 43 years) without re-exposure to
accident-related stimuli and on 64 age-matched healthy
subjects (M:FZ34:30; ages, 23–61 years; mean, 43 years).
PTSD patients were recruited from the PTSD clinic at
St Mary’s Hospital, The Catholic University of Korea. Their
traumatic events were all civil trauma including 18 motor
vehicle accidents, 3 domestic violence, and two physical
assaults by strangers. The mean time elapsed since the
traumatic events was 4.3G5.2 years. The diagnosis of
PTSD was established according to DSM-IV criteria
(American Psychiatric Association, 1994)usingthe
Structured Clin ical Interview for DSM-IV, administered
by a trained clinician. Clinician-Administered PTSD Scale
(CAPS) was administered to quantitatively characterize
PTSD symptoms. Their symptoms were moderate to severe
(mean and SD scores of CAPS: 87.9G12.7).
Subjects with a history of psychotic disorders or
dementia were excluded. The healthy controls had no self-
reported personal or familial psychiatric history. The
patients and controls were drug-free for at least 2 weeks
before this study. Brain MRI scanning was performed in all
patients and controls prior to the study in order to exclude
subjects with organic lesions such as hemorrhage, infarc-
tion, or tumor. No patient showed such findings, and thus no
one was excluded by this criterion. All subjects gave
written, informed consent to participate in the study. The
Human Subjects Committee at the Catholic Medical Center
approved the study.
2.2. SPECT procedure
SPECT imaging was initiated 20 min after intravenous
injection of approximately 740-925 MBq of Tc-99m ECD
using a multi-detector scanner (ECAM plus; Siemens,
Erlangen, Germany) equipped with a low-energy, fan-beam
collimator. The head unit consists of two rings of 59 probe-
type detectors. There is a rotating colli mator with septa
varying from 0 to 3.52 mm within the right of crystals. Both
the detector ring and the collimator rotate. Data were
acquired on 128!128 matrix size with a 20% symmetric
window at 140 keV. Continuous transaxial tomograms of
the brain were reconstructed after filtered back-projection
with a Butterworth (cutoff frequency 0.4 cycles/pix el,
order 5) to reduc e acquisition noise. Tc-99m ECD images
Y.A. Chung et al. / Clinical Neurophysiology 117 (2006) 637–642638
were corrected for tissue attenuation using a standard
Chang’s attenuation correction.
2.3. Image data analysis
For the analysis of SPECT imaging data, statistical
parametric mapping (SPM), a technique for making pixel-
by-pixel statistical comparisons between sets of images, was
used in this study. All subsequent image manipulation and
data analysis were performed on a personal computer using
a Windows 98 operating system (Microsoft, Redmond,
Wash, USA). The software for the image manipulation
included Matlab (ver. 5.3, Mathworks, Inc., Natick, MA)
and SPM99 software (Institute of Neurology, University
College of London, UK). The r aw SPECT data was
converted into the Analyze (Mayo Foundation, Baltimore,
MD, USA) format, using MRIcro software. The SPECT
data includes 348 bytes of header, 3.9 mm of x and y pixel
sizes, and 3.9 mm of slice thickness. The SPECT images of
the control group and PTSD patients were separately co-
registered into MNI SPECT template using the SPM method
in order to remove variations resulting from different sizes
and shapes of individual brains. The parameter s for co-
registration were intra-modality, linear algo rithm, 12 affine
parameter models for controlling the number of degrees of
freedom used in registration, and tri-linear interpolation. All
slices of a brain image were then resampled and averaged to
arrive at a mean pixel intensity, or the average pixel value of
the whole brain for that specific image. The intensity
threshold was set at 80% of the whole-brain mean. This
level eliminated low-intensity background noise inhe rent in
the images and effectively removed brain-edge halo caused
by partial-volume error, without losing any image data
specific to the brain. The global cerebra l blood flow rate was
normalized to an arbitrary mean of 50 ml/100 ml per minute
by a group-wise analysis of covariance (ANCOVA). The
data were then normalized to a better resolution SPECT
template (MNI template: Montreal Neurologi cal Institution
Template) and smoothed with 16 mm full with half
maximum (FWHM) prior to SPM analysis (Friston et al.,
1995) The final image format was 16-bit, with a size of 79!
95!68 and a voxel size of 2!2!2 mm. For the graphic
presentation of the results, sections were displayed as
transverse, sagittal, and coronal slices with a hot color map.
The normalized SPECT data from the investigation were
compared to a normal database constituted from 64 subjects
without morphological or neurological pathology for
detection of hypo- or hyperperfusion areas. After specifying
the appropriate desi gn matrix, changes in rCBF levels
produced by the different subject groups were estimated
according to the general linear model at each voxel. An
ANCOVA model was fitted, and a t statistic image (SPM[t])
for the contrast condi tion effect was constructed. The
resulting set of voxel t values constitutes the statistical
parametric mapping SPM[ t] with a threshold value of 4.80
(or PZ0.05, corrected) and a minimal cluster size of 50
voxels. The expected voxels per cluster were 12.128 and the
expected number of cluster was 0.05. The threshold of
cluster P value (corrected) was 0.026. For visualization of
the t score statistics, the t score voxel clusters were projected
onto the standard high-resolution MRI data set using the
projection protocol, which additionally displays the Talair-
ach coordinates, thus allowing anatomic identification. The
voxels with P-values of less than 0.05 were considered to be
significantly different.
3. Results
Compared with that of the control group, SPECT
imaging of PTSD patients showed increased uptake of
radiotracer in limbic regions, i.e. hippocampus, parahippo-
campal gyrus, anterior cingulate gyrus, isthmic portion of
the cingulate gyrus, and a portion of rhinencephalon
(Table 1). In addition, PTSD patients exhibited decreased
uptake of radiotracer in the left parietal angular gyrus, left
frontal precentral gyrus, left inferior temporal gyrus, and
right occipital sub-gyral white matter (Table 2). Fig. 1
shows maximum intensity projection images of difference s
of rCBF values between the two groups, indicating that
PTSD patients exhibited increased cerebral blood perfusion
in limbic regions and decreased perfusion in the superior
frontal gyrus, parietal and temporal regions, and occipital
sub-gyral white matter compared with those of the normal
Table 1
Brain regions with increased rCBF levels in PTSD patients compared with
those of normal controls
Brain regions Number of
voxels in
cluster
Voxel T x, y, z (mm)
Right cerebellum,
anterior lobe, culmen
1032 7.15 18, K36, K12
Right cerebrum, limbic
lobe, parahippocampal
gyrus, gray matter,
Brodmann area 36
5.39 26, K18, K24
Right cerebrum, frontal
lobe, sub-gyral
206 6.40 44, 12, K10
Right cerebrum, limbic
lobe, cingulate gyrus,
white matter
64 6.08 8, K16, 32
Left cerebrum,
sub-lobar, caudate, gray
matter, caudate body
143 6.01 K18, K18, K20
Left cerebrum, limbic
lobe, parahippocampal
gyrus, gray matter,
amygdala
5.50 K20, K8, K12
Left cerebrum, limbic
lobe, anterior cingulated
247 5.87 0, 16, K8
Left cerebrum,
sub-lobar, caudate, gray
matter, caudate body
5.52 K6, 14, 6
Y.A. Chung et al. / Clinical Neurophysiology 117 (2006) 637–642 639
controls. Fig. 2 shows the SPM images on the template, T1
weighed high-resolution brain MRI, which allows anatom-
ical identification of activation regions. This figure shows
more clearly that PTSD patients had increased rCBF in
limbic regions compared with those of the normal controls.
4. Discussion
We determined whether PTSD patients exhi bit altera-
tions in cerebral perfusion compared with age-match ed
normal subjects without re-expos ure to accident-related
stimuli. We found, using SPM analysis, that PTSD patients
showed alterations in cerebral blood perfusion under resting
conditions compared with normal controls over a number of
brain regions, in particular increased rCBF levels in limbic
regions and decreased rCBF levels in the superior frontal
gyrus and parietal and temporal regions. This result
indicates that PTSD patients have abnormal cerebral
perfusion levels in limbic regions and the frontal and
temporal cortex under resting conditions. This finding
supports the hypothesis of the involvement of li mbic
regions, which are thought to regulate emotion and memory,
in the pathophysiology of PTSD.
Sachinvala et al. (2000) also examined the changes in
rCBF involved in PTSD without re-exposure to accident-
related stimuli. They recorded Tc-99m hexamethyl propy-
lene amine oxime SPECT images from 17 PTSD patients
under resting conditions and found an increase in rCBF in
the cingulate regions, the temporal and parietal regions, the
caudate/putamen region, and the orbital and hippocampal
regions in PTSD patients compared with the control group.
There are some differences betwee n Sachinvala et al. (2000)
and our study: while they used the HMPAO in SPECT
analysis, we used Tc-99m ECD, which is reported to be a
better reflector of metabolism. Furthermore, some of
patients used in Sachinvala et al. (2000) took medications,
whereas patients in our study are all medication-free. Since
drugs may mask the true nature of the PTSD, it is possible
that the activation sites in their results are associated with
drug effects.
In addition, we used the SPM to analyze SPECT imaging
data, whereas previous studies have used conventional
region of interest (ROI) analysis (Sachinvala et al., 2000).
The conventional PET/SPECT imaging analysis requires
the application of a number of ROIs on the images, and
consequently ROI definition on functional images is time-
consuming. In addition, due to the subjectiveness and
propensity for individual operator bias, ROI analysis can be
less effective in accurately distin guishing regional vari-
ations between a set of images. We demonstrated in the
current study that SPM analysis is sensitive in detecting
alterations in rCBF levels and useful in investigating
alterations in rCBF levels in a patient group in comparison
with a control group under resting conditions.
The characteristic PTSD symptoms, such as intrusive
memories, flashbacks of the traumatic event, and hyperar-
ousal, suggest abnormalities in the regulation of emotion
and memory, thus implicating the limbic system as a
possible brain region associated with the diso rder. The
limbic system is known to play a critical role in the
regulation of emotions and in the storage and retrieval of
Table 2
Brain regions with decreased rCBF levels in PTSD patients compared with
normal controls
Brain regions Number of
voxels in cluster
Voxel T x, y, z (mm)
Left cerebrum, parietal
lobe, angular gyrus,
white matter
134 6.21 K42, K62, 30
Left cerebrum, frontal
lobe, precentral gyrus,
gray matter, Brodmann
area 6
142 6.19 K24, K12, 70
Left cerebrum, temporal
lobe, inferior temporal
gyrus, white matter
72 5.76 K50, K36, K18
Right cerebrum,
occipital lobe,
sub-gyral, white matter
50 5.58 26, K72, 28
Fig. 1. Maximum intensity projection images of (a) increased rCBF levels and (b) decreased rCBF levels in PTSD patients (nZ23) compared with normal
controls (nZ64).
Y.A. Chung et al. / Clinical Neurophysiology 117 (2006) 637–642640
memories. Previous PET and SPECT studies using
symptom provocation paradigms also support the hypoth-
esis of the involvement of limbic regions in the pathogenesis
of PTSD (Liberzon et al., 1999; Rauch et al., 1996; 1997;
Semple et al., 2000; Shin et al., 1997a,b; Zubieta et al.,
1999). For example, Liberzon et al. (1999) performed
SPECT imaging on patients with combat-related PTSD to
find an increased rCBF level in the amygdala and medial
prefrontal cortex during provocation. Hyperperfusion of
limbic and paralimbic regions may result from stress-
induced long-term potentiation through the monosynaptic
N-methyl-
D-aspartate (NMDA)-mediated pathway between
the amygdala and the periacqueductal grey (Hull, 2002). It
is possible that NMDA receptors can be activated to
produce long-term memories of events when a sufficient
amount of glutamate is released as a result of the stress
(Glue et al., 1993; Hull, 2002).
However, the main result of the current study is increased
rCBF levels in limbic regions in PTSD patients without re-
exposure to accident-r elated stimuli. This hyperperfusion of
limbic regions in PTSD during resting conditions might be
associated with the hyper-responsivity to accident-related
stimuli in PTSD patients. Another possibility is that an
increase in blood perfusion of limbic regions in PTSD
reflects ongoing psychological and psychophysiological
hyperfunction of overlearned survival response (or flash-
back response) in limbic regions. Silove (1998) hypoth-
esizes that a primitive learning center in the limbic system
rehearses traumatic memories following exposure to
trauma, thus inducing durable memories of the sources of
novel threat. According to this hypothesis, intrusive
phenomena like repetitive imagery represent an active
reworking of traum a memories at the cognitive level, a
process that helps the survivor to integrate the novel and
threatening information into new and expanded meaning
schemata which eventually provide a more accurate
representation of the posttrauma world. Thus, given that
hyperperfusion of limbic regions is associated with the
intrusive phenom ena of PTSD witho ut re-exposure to
accident-related stimuli, it possibly reflect an overlearned
survival response in patients in whom the putative limbic
rehearsal mechanism evades cortical control.
We also found a decrease in rCBF levels in the left
parietal angular gyrus, left frontal precentral gyrus , left
inferior temporal gyrus, and right occipital sub-gyral white
matter in PTSD patients. These findings are partially
consistent with those of previous imaging studies in patients
with PTSD, implicating dysfunction of governing cortices
(Hull, 2002; Shin et al., 2005). Particularly, decreasing
activities of the prefrontal cortex, which has a role in the
encoding and retrieval of verbal memory, appears to be
consistent with patients with PTSD having difficulty in
cognitively restructuring their traumatic experiences (Hull,
2002). Besides the prefrontal cortex, decreased parietal
blood flow has been reported in PTSD subjects compared
with healthy controls performing an attentional task
(Semple et al., 1996). Our previous EEG studies using
nonlinear dynamical methods also suggested that PTSD
patients have globally reduced complexity in their EEG
waveforms implicating their diffuse disturbed cortical
information processing (Chae et al., 2004). Although not
all functional imaging studies found the cortical dysfunction
and comorbid psychiatric illnesses, and differences in the
anxiety-provoking stimuli used in the imaging scans may
contribute to the inconsistency of findings in imaging
researches in those patients, the present study, which
suggests the higher cortical hypofunction and limbic
hyperactivation during the resting state, provides another
evidence for a reciprocal interaction between these two
regions in the path ophysiology of PTSD.
In summary, we showed that PTSD patients have
alterations in cerebral perfusion of limbic regions and
Fig. 2. (a) Axial, (b) coronal, and (c) sagittal SPM images on template T1 weighted high-resolution brain MRI. Brain regions of increased (red) and decreased
(blue) rCBF levels in PTSD patients (nZ23) compared with normal controls (nZ64) are shown.
Y.A. Chung et al. / Clinical Neurophysiology 117 (2006) 637–642 641
the frontal and temporal cortex without re-exposure to
accident-related stimuli compared with those of age-
matched healthy c ontrols. This finding suggests t he
involvement of limbic regi ons in the pathogenesis of PTSD.
Acknowledgements
This work was supported by the grants of the 2005
Nuclear R&D Plan Program (Study on the Radiation Brain
Science) of the Ministry of Science & Technology, South
Korea.
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    • "May 23, 2016particularly to working memory [22] . A perfusion study using SPECT showed decreased perfusion in the superior frontal gyrus of PTSD patients [23] . Meanwhile, fMRI studies have demonstrated that PTSD patients presented increased functional connectivity between the posterior cingulate cortex and the right superior frontal gyrus [24] as well as enhanced regional homogeneity in the left inferior parietal lobule and right superior frontal gyrus [25]. "
    [Show abstract] [Hide abstract] ABSTRACT: To explore the potential alterations in cerebral blood flow (CBF) and functional connectivity of recent onset post-traumatic stress disorder (PTSD) induced by a single prolonged trauma exposure, we recruited 20 survivors experiencing the same coal mining flood disaster as the PTSD (n = 10) and non-PTSD (n = 10) group, respectively. The pulsed arterial spin labeling (ASL) images were acquired with a 3.0T MRI scanner and the partial volume (PV) effect in the images was corrected for better CBF estimation. Alterations in CBF were analyzed using both uncorrected and PV-corrected CBF maps. By using altered CBF regions as regions-of-interest, seed-based functional connectivity analysis was then performed. While only one CBF deficit in right corpus callosum of PTSD patients was detected using uncorrected CBF, three more regions (bilateral frontal lobes and right superior frontal gyrus) were identified using PV-corrected CBF. Furthermore, the regional CBF of right superior frontal gyrus exhibited significantly negative correlation with the symptom severity (r = −0.759, p = 0.018). The resting-state functional connectivity analysis revealed increased connectivity between left frontal lobe and right parietal lobe. The results indicated the symptom-specific perfusion deficits and an aberrant connectivity in memory-related regions of PTSD patients when using PV-corrected ASL data. It also suggested that PV-corrected CBF exhibits more subtle changes that may be beneficial to perfusion and connectivity analysis.
    Full-text · Article · May 2016
    Yang LiuYang LiuBaojuan LiBaojuan LiNa FengNa Feng+1more author...[...]
    • "Like other addictions, the severity of alcoholism is exacerbated by stress [3][4][5][6], however the mechanisms of this underlying interaction are not fully understood. Those with PTSD and alcoholics display abnormal striatal activity [7][8][9][10][11][12], suggesting dysregulated striatal neuroplasticity may underlie the effects of PTSD on alcohol-associated addictive behaviors. The endocannabinoid system, including cannabinoid receptor-1 (CB1) and its endogenous endocannabinoid ligands, anandamide and 2-arachidonoylglycerol (2-AG), is an important modulator of dorsal striatal neuroplasticity and has known involvement in fear processing and PTSD diagnoses. "
    [Show abstract] [Hide abstract] ABSTRACT: Impaired striatal neuroplasticity may underlie increased alcoholism documented in those with posttraumatic stress disorder (PTSD). Cannabinoid receptor-1 (CB1) is sensitive to the effects of ethanol (EtOH) and traumatic stress, and is a critical regulator of striatal plasticity. To investigate CB1 involvement in the PTSD-alcohol interaction, this study measured the effects of traumatic stress using a model of PTSD, mouse single-prolonged stress (mSPS), on EtOH-induced locomotor sensitization and striatal CB1 levels.
    Full-text · Article · May 2016
    • "There are however several potential pathways that may explain the association between shift work history and cognitive performance. For instance, human and animal studies have shown that psychological stress conditions exert multiple adverse effects on the frontal lobe of the brain, comprising diminished blood perfusion (Chung et al., 2006), reduced grey matter volume (Li et al., 2014), and compromised neural plasticity (Zheng et al., 2011). Given that frontal lobe functions play an important role for the performance on the TMT (Stuss and Levine, 2002), it could be hypothesized that stress may account for the observed association between shift work and performance on this test. "
    [Show abstract] [Hide abstract] ABSTRACT: Shift work has been proposed to promote cognitive disturbances in humans; however, conflicting evidence is also present. By utilizing data from 7,143 middle-aged and elderly humans (45-75 years) who participated in the Swedish EpiHealth cohort study, the present analysis sought to investigate whether self-reported shift work history would be associated with performance on the trail making test (TMT). The TMT has been proposed to be a useful neuropsychological tool to evaluate humans’ executive cognitive function, which is known to decrease with age. Following adjustment for potential confounders (e.g. age, education, and sleep duration), it was observed that current and recent former shift workers (worked shifts during the past 5 years) performed worse on the TMT than non-shift workers. In contrast, performance on the TMT did not differ between past shift workers (off from shift work for more than 5 years) and non-shift workers. Collectively, our results indicate that shift work history is linked to poorer performance on the TMT in a cohort of middle-aged and elderly humans.
    Full-text · Article · May 2016
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