Neuroanatomical features in soldiers with post-traumatic stress disorder

BackgroundPosttraumatic stress disorder (PTSD), an anxiety disorder that can develop after exposure to psychological trauma, impacts up to 20 % of soldiers returning from combat-related deployment. Advanced neuroimaging holds diagnostic and prognostic potential for furthering our understanding of its etiology. Previous imaging studies on combat-related PTSD have focused on selected structures, such as the hippocampi and cortex, but none conducted a comprehensive examination of both the cerebrum and cerebellum. The present study provides a complete analysis of cortical, subcortical, and cerebellar anatomy in a single cohort. Forty-seven magnetic resonance images (MRIs) were collected from 24 soldiers with PTSD and 23 Control soldiers. Each image was segmented into 78 cortical brain regions and 81,924 vertices using the corticometric iterative vertex based estimation of thickness algorithm, allowing for both a region-based and a vertex-based cortical analysis, respectively. Subcortical volumetric analyses of the hippocampi, cerebellum, thalamus, globus pallidus, caudate, putamen, and many sub-regions were conducted following their segmentation using Multiple Automatically Generated Templates Brain algorithm.ResultsParticipants with PTSD were found to have reduced cortical thickness, primarily in the frontal and temporal lobes, with no preference for laterality. The region-based analyses further revealed localized thinning as well as thickening in several sub-regions. These results were accompanied by decreased volumes of the caudate and right hippocampus, as computed relative to total cerebral volume. Enlargement in several cerebellar lobules (relative to total cerebellar volume) was also observed in the PTSD group.ConclusionsThese data highlight the distributed structural differences between soldiers with and without PTSD, and emphasize the diagnostic potential of high-resolution MRI.

[1]  I. Liberzon,et al.  The Neurocircuitry of Fear, Stress, and Anxiety Disorders , 2011, Neuropsychopharmacology.

[2]  Alan C. Evans,et al.  Automatic "pipeline" analysis of 3-D MRI data for clinical trials: application to multiple sclerosis , 2002, IEEE Transactions on Medical Imaging.

[3]  A. Braun,et al.  The neural organization of discourse: an H2 15O-PET study of narrative production in English and American sign language. , 2001, Brain : a journal of neurology.

[4]  D. Louis Collins,et al.  Automatic 3‐D model‐based neuroanatomical segmentation , 1995 .

[5]  L. Duan,et al.  Abnormal cerebellum density in victims of rape with post‐traumatic stress disorder: Voxel‐based analysis of magnetic resonance imaging investigation , 2010 .

[6]  I. Liberzon,et al.  Biological studies of post-traumatic stress disorder , 2012, Nature Reviews Neuroscience.

[7]  M. Fredrikson,et al.  Brain function in a patient with torture related post-traumatic stress disorder before and after fluoxetine treatment: a positron emission tomography provocation study , 2001, Neuroscience Letters.

[8]  Dewen Hu,et al.  Gray matter density reduction in the insula in fire survivors with posttraumatic stress disorder: A voxel-based morphometric study , 2006, Psychiatry Research: Neuroimaging.

[9]  E. Irle,et al.  Hippocampal volume in adult burn patients with and without posttraumatic stress disorder. , 2004, The American journal of psychiatry.

[10]  Gregor Hasler,et al.  Atypical visual processing in posttraumatic stress disorder , 2013, NeuroImage: Clinical.

[11]  F. Woermann,et al.  Posttraumatic stress disorder and fMRI activation patterns of traumatic memory in patients with borderline personality disorder , 2004, Biological Psychiatry.

[12]  Rainer Goebel,et al.  Thinner prefrontal cortex in veterans with posttraumatic stress disorder , 2008, NeuroImage.

[13]  Lisa A. Thomas,et al.  Pituitary volumes in pediatric maltreatment-related posttraumatic stress disorder , 2004, Biological Psychiatry.

[14]  Lino Becerra,et al.  Functional Neuroimaging of Reward Circuitry Responsivity to Monetary Gains and Losses in Posttraumatic Stress Disorder , 2009, Biological Psychiatry.

[15]  V. Magnotta,et al.  Hippocampal volume in chronic posttraumatic stress disorder (PTSD): MRI study using two different evaluation methods. , 2006, Journal of affective disorders.

[16]  Marnie E. Shaw,et al.  Cerebral function in posttraumatic stress disorder during verbal working memory updating: a positron emission tomography study , 2003, Biological Psychiatry.

[17]  M. Shenton,et al.  Smaller hippocampal volume predicts pathologic vulnerability to psychological trauma , 2002, Nature Neuroscience.

[18]  R. Yehuda Are glucocortoids responsible for putative hippocampal damage in PTSD? How and when to decide , 2001, Hippocampus.

[19]  C. Sripada,et al.  The functional neuroanatomy of PTSD: a critical review. , 2008, Progress in brain research.

[20]  Anjen Chenn,et al.  Regulation of Cerebral Cortical Size by Control of Cell Cycle Exit in Neural Precursors , 2002, Science.

[21]  E. Vermetten,et al.  Stress hormones and post traumatic stress disorder : basic studies and clinical perspectives , 2008 .

[22]  G. Hazlett,et al.  Reward circuitry in resilience to severe trauma: An fMRI investigation of resilient special forces soldiers , 2009, Psychiatry Research: Neuroimaging.

[23]  J. Naglieri,et al.  Using IQ Discrepancy Scores To Examine the Neural Correlates of Specific Cognitive Abilities , 2013, The Journal of Neuroscience.

[24]  N. Breslau,et al.  Intelligence and other predisposing factors in exposure to trauma and posttraumatic stress disorder: a follow-up study at age 17 years. , 2006, Archives of general psychiatry.

[25]  Wang Zhan,et al.  Patterns of altered cortical perfusion and diminished subcortical integrity in posttraumatic stress disorder: An MRI study , 2011, NeuroImage.

[26]  M. Kuchibhatla,et al.  Cerebellar Volumes in Pediatric Maltreatment-Related Posttraumatic Stress Disorder , 2006, Biological Psychiatry.

[27]  H. Critchley,et al.  Cerebral correlates of autonomic cardiovascular arousal: a functional neuroimaging investigation in humans , 2000, The Journal of physiology.

[28]  D. Yang,et al.  Alterations in cerebral perfusion in posttraumatic stress disorder patients without re-exposure to accident-related stimuli , 2006, Clinical Neurophysiology.

[29]  Viola Vaccarino,et al.  Magnetic resonance imaging (MRI) measurement of hippocampal volume in posttraumatic stress disorder: a meta-analysis. , 2005, Journal of affective disorders.

[30]  Loretta S. Malta,et al.  A meta-analysis of structural brain abnormalities in PTSD , 2006, Neuroscience & Biobehavioral Reviews.

[31]  Alan C. Evans,et al.  Cortical thickness analysis examined through power analysis and a population simulation , 2005, NeuroImage.

[32]  C. Weems,et al.  IQ and Posttraumatic Stress Symptoms in Children Exposed to Interpersonal Violence , 2006, Child psychiatry and human development.

[33]  C. Nemeroff,et al.  PAGES_ 12_AG_1004_BA.qxd:DCNS#50 , 2011 .

[34]  P. Basser Diffusion MRI: From Quantitative Measurement to In vivo Neuroanatomy , 2009 .

[35]  J. Bremner 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 , 2001, Hippocampus.

[36]  T. Tanielian,et al.  Invisible Wounds of War Psychological and Cognitive Injuries, Their Consequences, and Services to Assist Recovery , 2022 .

[37]  R. Kikinis,et al.  Magnetic resonance imaging study of hippocampal volume in chronic, combat-related posttraumatic stress disorder , 1996, Biological Psychiatry.

[38]  Alan C. Evans,et al.  Intellectual ability and cortical development in children and adolescents , 2006, Nature.

[39]  Uta Sailer,et al.  Altered reward processing in the nucleus accumbens and mesial prefrontal cortex of patients with posttraumatic stress disorder , 2008, Neuropsychologia.

[40]  Y. Benjamini,et al.  THE CONTROL OF THE FALSE DISCOVERY RATE IN MULTIPLE TESTING UNDER DEPENDENCY , 2001 .

[41]  Cathy L Pederson,et al.  Hippocampal Volume and Memory Performance in a Community-Based Sample of Women with Posttraumatic Stress Disorder Secondary to Child Abuse , 2004, Journal of traumatic stress.

[42]  Jeffrey L. Birk,et al.  Reduced caudate and nucleus accumbens response to rewards in unmedicated individuals with major depressive disorder. , 2009, The American journal of psychiatry.

[43]  M. Phillips,et al.  Post-traumatic stress symptoms correlate with smaller subgenual cingulate, caudate, and insula volumes in unmedicated combat veterans , 2012, Psychiatry Research: Neuroimaging.

[44]  Alan C. Evans,et al.  A nonparametric method for automatic correction of intensity nonuniformity in MRI data , 1998, IEEE Transactions on Medical Imaging.

[45]  D. Collins,et al.  Performing label‐fusion‐based segmentation using multiple automatically generated templates , 2013, Human brain mapping.

[46]  Kathryn A. Moores,et al.  Abnormal frontal and parietal activity during working memory updating in post-traumatic stress disorder , 2005, Psychiatry Research: Neuroimaging.

[47]  S. Rauch,et al.  Evidence for Acquired Pregenual Anterior Cingulate Gray Matter Loss from a Twin Study of Combat-Related Posttraumatic Stress Disorder , 2008, Biological Psychiatry.

[48]  Alan C. Evans,et al.  Automated 3-D extraction and evaluation of the inner and outer cortical surfaces using a Laplacian map and partial volume effect classification , 2005, NeuroImage.

[49]  N. Tzourio-Mazoyer,et al.  Automated Anatomical Labeling of Activations in SPM Using a Macroscopic Anatomical Parcellation of the MNI MRI Single-Subject Brain , 2002, NeuroImage.

[50]  D. Louis Collins,et al.  Towards accurate, automatic segmentation of the hippocampus and amygdala from MRI by augmenting ANIMAL with a template library and label fusion , 2010, NeuroImage.

[51]  M. Corbetta,et al.  The Reorienting System of the Human Brain: From Environment to Theory of Mind , 2008, Neuron.

[52]  Marijn C. W. Kroes,et al.  Structural brain abnormalities common to posttraumatic stress disorder and depression. , 2011, Journal of psychiatry & neuroscience : JPN.

[53]  C. Wotjak,et al.  Biomarkers in Posttraumatic Stress Disorder: Overview and Implications for Future Research , 2013, Disease markers.

[54]  Robert F. Hevner,et al.  Role of Intermediate Progenitor Cells in Cerebral Cortex Development , 2007, Developmental Neuroscience.

[55]  Philip D. Harvey,et al.  Learning and Memory in Aging Combat Veterans with PTSD , 2005, Journal of clinical and experimental neuropsychology.

[56]  Impairment of Emotional Facial Expression and Prosody Discrimination Due to Ischemic Cerebellar Lesions , 2014, The Cerebellum.

[57]  M E Shenton,et al.  Longitudinal MRI study of hippocampal volume in trauma survivors with PTSD. , 2001, The American journal of psychiatry.

[58]  Alan C. Evans,et al.  Measurement of Cortical Thickness Using an Automated 3-D Algorithm: A Validation Study , 2001, NeuroImage.

[59]  H. Yamasue,et al.  Voxel-based analysis of MRI reveals anterior cingulate gray-matter volume reduction in posttraumatic stress disorder due to terrorism , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[60]  A. Starcevic,et al.  Volume Changes of Corpus Striatum, Thalamus, Hippocampus and Lateral Ventricles in Posttraumatic Stress Disorder (PTSD) Patients Suffering from Headaches and without Therapy , 2010, Central European neurosurgery.

[61]  S. Kéri,et al.  Reduced hippocampal volume is associated with overgeneralization of negative context in individuals with PTSD. , 2015, Neuropsychology.

[62]  C. Fennema-Notestine,et al.  Brain morphometry in female victims of intimate partner violence with and without posttraumatic stress disorder , 2002, Biological Psychiatry.

[63]  R. Yehuda POST-TRAUMATIC STRESS DISORDER , 1985, The Lancet.