Thinner prefrontal cortex in veterans with posttraumatic stress disorder
Introduction
Neuroimaging studies in posttraumatic stress disorder (PTSD) have identified a number of functional and structural alterations that are associated with this disorder. Structural neuroimaging studies in PTSD have focused primarily on manual based hippocampal volumetry. These studies have shown that patients with PTSD are associated with bilateral smaller hippocampal volume (Geuze et al., 2005, Kitayama et al., 2005). A recent meta-analysis, confirmed the presence of significantly smaller hippocampal volumes and left amygdala volumes in patients with PTSD compared to controls with and without trauma exposure (Karl et al., 2006).
However, while considerable attention has been placed on volume changes in subcortical structures, very little attention has been directed to grey matter reductions in the cortex. Manual tracing of the anterior cingulate cortex has shown that this area is also smaller in patients with PTSD compared to controls (Woodward et al., 2006, Rauch et al., 2003). Several voxel-based morphometry studies, a whole-brain analysis technique, have been applied in PTSD. These studies have shown reduced grey matter density in the anterior cingulate gyrus, hippocampus, and insula (Chen et al., 2006, Corbo et al., 2005, Yamasue et al., 2003, Kasai et al., 2007). A recent meta-analysis of these studies confirmed that patients with PTSD revealed significantly smaller anterior cingulate cortex volume compared to trauma-exposed controls (Karl et al., 2006). In pediatric patients with PTSD, significantly smaller prefrontal lobe volume and corpus callosum volume have been found (De Bellis et al., 1999, De Bellis et al., 2002b). The findings of smaller corpus callosum volume have not been replicated in a sample of adult patients with PTSD (Kitayama et al., 2007). Functional neuroimaging studies have also identified a number of brain areas with altered activity in patients with PTSD, including the prefrontal cortex, temporal cortex, insula, amygdala, and hippocampus (Francati et al., 2007, Nemeroff et al., 2006, Hull, 2002).
Cortical thickness and volumetric analysis receive increasing interest in the imaging community because it allows relation of cognitive abilities, effects of aging, and effects of diseases to (subtle) structural changes in the brain. Practical constraints, however, related to intensive measurement technique and the use of postmortem samples, make it difficult to compare differences in cytoarchitecture across the cortex. Whole brain volumetric techniques are also compromised by large inter-individual differences in neuroanatomy making it difficult to match the same macroscopic regions between subjects. Recent advances in computational analysis, provide new opportunities to use imaging data to derive more knowledge on cortical thickness. In this study, we have applied the new cortical thickness analysis tools in Brainvoyager QX to compare veterans with PTSD to veterans without PTSD. In order to maximize the spatial correspondence mapping between cortical macrostructures, we also made use of the new technique of cortex-based alignment, which aligns reconstructed cortices using curvature information reflecting the gyral/sulcal folding pattern. It has been shown that a cortical matching approach substantially improves statistical analysis across subjects by reducing anatomical variability (Fischl et al., 1999a, Fischl et al., 1999b, Dale et al., 1999).
In this study our goal was to employ this relatively new technique to examine cortical thickness in patients with PTSD. We hypothesized that patients with PTSD would reveal reduced cortical thickness in frontal and temporal brain areas. Due to technical limitations of the cortical thickness algorithm, which performed less accurately in the inferior temporal lobe, and medial prefrontal cortex, we only examined cortical thickness in the bilateral superior, middle, and inferior frontal gyri, as well as the bilateral superior and middle temporal gyri.
Section snippets
Subjects
The sample consisted of twenty-five male Dutch veterans with PTSD, and twenty-five age matched control veterans without PTSD. All patients were recruited from the Department of Military Psychiatry at the Central Military Hospital in Utrecht. Control subjects were recruited via direct mail to veterans who were registered at the Veterans Institute in Doorn, The Netherlands. All participants had served in UN peacekeeping missions in Lebanon, Cambodia, or Bosnia. Control veterans were matched to
Psychometric data
PTSD patients and control veterans were matched with respect to age, gender, time since trauma, year, and region of deployment. There were also no significant differences in years of education between the two groups. Patients with PTSD had significantly greater CAPS, Hamilton A, and Hamilton D scores, (see Table 1). According to the SCID, the PTSD group met lifetime (past) DSM-IV (American Psychiatric Association 1994) diagnostic criteria for the following disorders: major depressive disorder (n
Discussion
This is the first study in the field of PTSD that provides data on the cortical thickness of veterans with PTSD compared to healthy control veterans. Cortical thickness is a relatively new semi-automatic technique that has recently also been implemented in the neuroimaging program Brainvoyager QX 1.7. In this ROI based analysis, patients revealed reduced cortical thickness in the bilateral prefrontal cortex and the left superior temporal gyrus compared to controls.
In PTSD several different
Acknowledgments
This work was financially supported by the Dutch Ministry of Defence. The authors would also like to thank the Radiology Department of Utrecht University Medical Centre for acquisition of MRI scans, and Arthur Rademaker, MSc for clinical assessments.
References (54)
- et al.
Neural correlates of exposure to traumatic pictures and sound in Vietnam combat veterans with and without posttraumatic stress disorder: a positron emission tomography study
Biol. Psychiatry
(1999) - et al.
Neural correlates of the classic color and emotional stroop in women with abuse-related posttraumatic stress disorder
Biol. Psychiatry
(2004) - et al.
Corticolimbic blood flow in posttraumatic stress disorder during script-driven imagery
Biol. Psychiatry
(2005) - et al.
Gray matter density reduction in the insula in fire survivors with posttraumatic stress disorder: a voxel-based morphometric study
Psychiatry Res.
(2006) - et al.
Cerebral function in posttraumatic stress disorder during verbal working memory updating: a positron emission tomography study
Biol. Psychiatry
(2003) - et al.
Size versus shape differences: contrasting voxel-based and volumetric analyses of the anterior cingulate cortex in individuals with acute posttraumatic stress disorder
Biol. Psychiatry
(2005) - et al.
Cortical surface-based analysis. I. Segmentation and surface reconstruction
NeuroImage
(1999) - et al.
A.E. Bennett Research Award. Developmental traumatology. Part II: Brain development
Biol. Psychiatry
(1999) - et al.
Superior temporal gyrus volumes in maltreated children and adolescents with PTSD
Biol. Psychiatry
(2002) - et al.
Brain structures in pediatric maltreatment-related posttraumatic stress disorder: a sociodemographically matched study
Biol. Psychiatry
(2002)
Cortical surface-based analysis. II: Inflation, flattening, and a surface-based coordinate system
NeuroImage
Cortex-based independent component analysis of fMRI time series
Magn. Reson. Imaging
Mapping IQ and gray matter density in healthy young people
NeuroImage
A meta-analysis of structural brain abnormalities in PTSD
Neurosci. Biobehav. Rev.
Magnetic resonance imaging (MRI) measurement of hippocampal volume in posttraumatic stress disorder: a meta-analysis
J. Affect. Disord.
Brain activation during script-driven imagery induced dissociative responses in PTSD: a functional magnetic resonance imaging investigation
Biol. Psychiatry
Cerebral blood flow changes during script-driven imagery in police officers with posttraumatic stress disorder
Biol. Psychiatry
Cortical thinning in cingulate and occipital cortices in first episode schizophrenia
Biol. Psychiatry
Posttraumatic stress disorder: a state-of-the-science review
J. Psychiatr. Res.
Neurocircuitry models of posttraumatic stress disorder and extinction: human neuroimaging research — past, present, and future
Biol. Psychiatry
Abnormal frontal and parietal activity during working memory updating in post-traumatic stress disorder
Psychiatry Res.
Decreased anterior cingulate volume in combat-related PTSD
Biol. Psychiatry
The development of a Clinician-Administered PTSD Scale
J. Trauma Stress
Learning and retrieval rate of words presented auditorily and visually
J. Gen. Psych.
Hypotheses and controversies related to effects of stress on the hippocampus: an argument for stress-induced damage to the hippocampus in patients with posttraumatic stress disorder
Hippocampus
Positron emission tomography measurement of cerebral metabolic correlates of yohimbine administration in combat-related posttraumatic stress disorder
Arch. Gen. Psychiatry
Decreased benzodiazepine receptor binding in prefrontal cortex in combat-related posttraumatic stress disorder
Am. J. Psychiatry
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