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Understanding Neuropsychiatric Disorders
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Book description

An informative and comprehensive review from the leading researchers in the field, this book provides a complete one-stop guide to neuroimaging techniques and their application to a wide range of neuropsychiatric disorders. For each disorder or group of disorders, separate chapters review the most up-to-date findings from structural imaging, functional imaging and/or molecular imaging. Each section ends with an overview from a internationally-renowned luminary in the field, addressing the question of 'What do we know and where are we going?' Richly illustrated throughout, each chapter includes a 'summary box', providing readers with explicit take-home messages. This is an essential resource for clinicians, researchers and trainees who want to learn how neuroimaging tools lead to new discoveries about brain and behaviour associations in neuropsychiatric disorders.

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Contents

Page 1 of 2

Contents
  • Section I - Schizophrenia
  • View abstract

    Summary

    This chapter provides a review of the vast body of published research that has used either structural magnetic resonance imaging (MRI) or diffusion tensor imaging (DTI) to investigate for neuroanatomical abnormalities in schizophrenia (SZ) patients. If one thing is clear from the multitude of MRI and DTI studies reviewed in the chapter, it is that there is now a great deal of evidence indicating that SZ patients exhibit consistent (albeit subtle) and widespread abnormalities in both their gray matter (GM) and white matter (WM). An important question, then, is whether these GM and WM abnormalities have separate causes, or whether they share a common underlying pathology. A highly speculative theory is presented as to how a single mechanism could potentially underlie the GM abnormalities, WM abnormalities, hyperdopaminergia and psychotic features characteristic of SZ. This theory is extremely speculative and would benefit from a great deal more supporting empirical evidence.
  • 2 - Functional imaging of schizophrenia
    pp 30-47
    • By Godfrey D. Pearlson, Olin Neuropsychiatry Research Center Institute of Living Hartford, CT, USA and Department of Psychiatry Yale University School of Medicine New Haven, CT, USA
  • View abstract

    Summary

    Functional magnetic resonance imaging (fMRI) neuroimaging investigations in schizophrenia have been used for a variety of purposes. Cognitive-based designs are generally chosen, so that particular brain regions or circuits could be specifically probed. In recent years novel analysis methods have enabled much useful information to be extracted from the type of taskless design that was generally abandoned for PET imaging in the 1980s. Independent component analysis (ICA) is used to identify temporally coherent networks. Some investigators have also started with active positive clinical symptoms, for example hallucinations. Human versions of the hippocampally dependent Morris water task assess allocentric navigation, or three-dimensional mazes, that can be presented as virtual-reality tasks in the fMRI scanner. New discoveries in the genetics of schizophrenia have begun to have more impact on functional neuroimaging research. Parallel independent component analysis (para-ICA) is used to identify simultaneously independent components of imaging and genetic modalities.
  • 3 - Spectroscopic imaging of schizophrenia
    pp 48-77
    • By Jay W. Pettegrew, Departments of Psychiatry, Neurology, Behavioral and Community Health Sciences, University of Pittsburgh School of Medicine and Department of Bioengineering University of Pittsburgh Pittsburgh, PA, USA, Richard J. McClure, Department of Psychiatry University of Pittsburgh School of Medicine Pittsburgh, PA, USA, Kanagasabai Panchalingam, Department of Psychiatry University of Pittsburgh School of Medicine Pittsburgh, PA, USA
  • View abstract

    Summary

    This chapter addresses fundamental technological considerations followed by a discussion of what molecular and metabolic information can be obtained from 31P and 1H magnetic resonance spectroscopy (MRS). This is followed by a selective review of the literature to date on 31P and 1H MRS studies in schizophrenia. In a proton-coupled in-vivo 31P brain spectrum, the resonances that are reliably quantifiable include phosphomonoester (PME), inorganic orthophosphate (Pi), phosphodiester (PDE), phosphocreatine (PCr), γ-adenosine-50-triphosphate (γATP), αATP, and βATP. The PME and PDE levels from the short nuclear magnetic resonance (NMR) correlation time components provide a measure of membrane phospholipid metabolism. The in-vivo 1H MRS spectrum contains three major resonance regions. Many neurochemical, neuropathological and functional imaging studies have implicated the frontotemporal neural networks in schizophrenia. Most of the in-vivo 1H MRS findings in schizophrenia focus on changes in N-acetyl aspartate (NAA), the largest resonance in 1H MRS spectra.
  • 4 - Neuroreceptor imaging of schizophrenia
    pp 78-87
    • By Dean F. Wong, The Russel H. Morgan Department of Radiology and Radiological Science The Johns Hopkins University School of Medicine Baltimore, MD, USA, James Robert Brašić, The Russell H. Morgan Department of Radiology and Radiological Science The Johns Hopkins University School of Medicine Baltimore, MD, USA, Nicola Cascella, Department of Psychiatry and Behavioral Sciences The Johns Hopkins University School of Medicine Baltimore, MD, USA
  • View abstract

    Summary

    Neuroreceptor imaging has a major role in aiding how to administer a clinically effective drug dose that minimizes dose-dependent side effects. Considerable lines of evidence converge to confirm that alterations in the density, distribution, and function of dopamine D2/D3 receptors in the brain play a role in the pathophysiology of schizophrenia. Positron emission tomography (PET)/single-photon emission computed tomography (SPECT) receptor occupancy allows determination of the likely optimal dose of dopamine D2 receptor blocking drugs to produce a therapeutic effect with minimal adverse effects. Pharmacological challenges are one of the most promising areas in in-vivo neuronal receptor imaging to alter neurotransmitters levels. Serotonin is the second major neurotransmitter system studied in schizophrenia. Glutamate, the excitatory neurotransmitter, likely has multiple roles in the pathogenesis and pathology of schizophrenia. A novel approach to the treatment of schizophrenia is the use of anti-psychotic medication.
  • 5 - Neuroimaging of schizophrenia: commentary
    pp 88-92
    • By Nancy Andreasen, Department of Psychiatry University of Iowa Iowa City, IA, USA
  • View abstract

    Summary

    Neuroimaging technologies have revolutionized the capacity to study schizophrenia and the understanding of its neural substrates and neural mechanisms. This chapter enables the reader to take stock of how far we have in fact come. It focuses on the developments of neuroimaging of schizophrenia till 1970s, from the mid-1980s till the mid-1990s, and the present modern era. By the early 1980s, a thrilling new imaging technology emerged: magnetic resonance imaging (MRI). The technical challenges of positron emission tomography (PET), the need for a cyclotron and a radiochemist, and design limitations imposed by repeated radiation exposure prevented the functional imaging modality from becoming widely available. In the world of MR spectroscopy (MRS), a future goal is to develop the MR sequences and the analysis tools for conducting whole-brain MRS. In the world of fMR, goals include methods to measure blood flow and metabolism rather than the BOLD effect.
  • Section II - Mood Disorders
  • View abstract

    Summary

    This chapter discusses recent structural neuroimaging studies that address the regions of interest in the proposed anterior limbic network model. Given the predominance of MRI in structural imaging of psychiatric disorders, the chapter also focuses on this imaging modality. First, longitudinal studies are needed to clarify how brain structures change within individual patients, with particular regard to the corresponding course of illness. Second, more sophisticated measures, such as diffusion tensor imaging (DTI) tractography or shape analyses, may more consistently define the subtle structural abnormalities that are likely in bipolar disorder and that may be missed with less-specific measures. Third, studies in young patients are critical given the typical adolescent onset of bipolar disorder and early course progression. Finally, integrating structural imaging with functional and neurochemical are the only ways to move morphometric imaging from high-priced and sophisticated phrenology to a better understanding of the neural basis of bipolar disorder.
  • 7 - Functional imaging of bipolar illness
    pp 109-124
    • By William M. Marchand, Department of Psychiatry University of Utah School of Medicine Salt Lake City, UT, USA, Deborah A. Yurgelun-Todd, Department of Psychiatry Salt Lake City VA Healthcare System and Department of PsychiatryUniversity of Utah School of Medicine Salt Lake City, UT, USA
  • View abstract

    Summary

    This chapter reviews functional neuroimaging findings in the dorsal and ventral systems, as well as in other brain regions. Multiple functional imaging studies indicate basal ganglia dysfunction in bipolar disorder (BD). The chapter provides a more generalized review of functional abnormalities of the prefrontal cortex (PFC) in BD. Several functional magnetic resonance imaging (fMRI) studies have demonstrated primary motor cortex and supplementary motor area (SMA) dysfunction in BD. Functional imaging studies of pediatric BD to date have found evidence of abnormalities of the dorsal and ventral emotional control systems as well as other brain regions also implicated in adult BD. The studies reviewed in the chapter provide compelling evidence of dorsal and ventral system dysregulation in BD. The chapter provides considerable evidence of dysfunction in other brain regions including temporal, posterior cingulate, motor, parietal, occipital, and cerebellar regions. Most studies have examined medicated subjects, which introduce a significant potential confound.
  • 8 - Molecular imaging of bipolar illness
    pp 125-138
    • By John O. Brooks III, Department of Psychiatry David Geffen School of Medicine University of California, Los Angeles Los Angeles, CA, USA, Po W. Wang, Department of Psychiatry Mount Sinai School of Medicine New York, NY, USA and Medical Department Brookhaven National Laboratory Upton, NY, USA, Terence A. Ketter, Department of Psychiatry and Behavioral Sciences Stanford University School of Medicine Stanford, CA, USA
  • View abstract

    Summary

    There are a number of potential neurochemical alterations in the dorsolateral prefrontal circuit that are related to the clinical expression of bipolar disorder. This chapter focuses on translational studies that integrate neurochemical and neuroanatomical information to better understand the pathophysiology of bipolar disorders. There are three major frontal-subcortical circuits that constitute the corticolimbic network: dorsolateral prefrontal, lateral orbitofrontal, and anterior cingulate. Several techniques have been developed that allow for non-invasive assessment of neurochemistry. Ligand-specific positron emission tomography (PET) and single photon emission computed tomography (SPECT) permit regional measurement of monoamines and other neurochemicals, which are thought to be crucial to affective processes. There have been numerous findings of peripheral serotonergic dysfunction in bipolar disorder, including decreased serotonergic reuptake in platelets. The neurochemistry of corticolimbic circuits presents additional challenges for clarifying the neurochemical basis of dysregulation that has been observed in functional neuroimaging studies.
  • 9 - Structural imaging of major depression
    pp 139-150
    • By Anand Kumar, Department of Psychiatry University of Illinois at Chicago Chicago, IL, USA, Olusola Ajilore, Department of Psychiatry University of Illinois at Chicago Chicago, IL, USA
  • View abstract

    Summary

    Structural imaging studies in major depression have identified volume alterations in prefrontal cortex, hippocampus, amygdala, and basal ganglia structures. This chapter reviews structural imaging findings in major depression focusing on magnetic resonance imaging (MRI) methodologies such as volumetric analysis, shape analysis, magnetization transfer (MT), and diffusion tensor imaging (DTI). White matter hyperintensities have been seen in periventricular, deep white matter and subcortical regions in association with major depression. More subtle white matter alterations have been detected with DTI and MT, suggestive of microstructural abnormalities, even in normal-appearing white matter. Another quantification technique measures the average diffusion of water in a voxel and can be expressed as the apparent diffusion coefficient (ADC). Several studies have used DTI to examine microstructural changes in white matter that appears normal using more conventional MRI techniques. The chapter explores the pathological and cognitive correlates, as well as the clinical significance of these structural findings.
  • 10 - Functional imaging of major depression
    pp 151-169
    • By Simon A. Surguladze, Institute of Psychiatry King's College London London, UK, Mary L. Phillips, Department of Psychiatry University of Pittsburgh School of Medicine Pittsburgh, PA, USA
  • View abstract

    Summary

    This chapter focuses on recent developments in functional neuroimaging that have highlighted functional abnormalities in key neural regions and neural systems underlying different executive control and emotional processes that are impaired in major depressive disorder (MDD). It then turns to findings from studies that employed functional neuroimaging techniques to examine functional neural abnormalities during rest, executive control and emotional challenge in individuals with MDD during depressed episode. The chapter describes new directions in functional neuroimaging of MDD, including functional neuroimaging studies. It also examines the newer neuroimaging analysis techniques that can be employed in the study of MDD, including functional and resting-state connectivity analyses. The chapter presents an integration of the major findings from these studies that have led to the development of neural models of MDD. Finally, it highlights the key neural system functional abnormalities that may represent potential biomarkers of MDD.
  • 11 - Molecular imaging of major depression
    pp 170-196
    • By Julia Sacher, PET Centre Centre for Addiction and Mental Health Toronto, ON, Canada, Gwenn S. Smith, Department of Psychiatry and Behavioral Sciences The Johns Hopkins University School of Medicine Baltimore, MD, USA
  • View abstract

    Summary

    The primary focus of radiochemistry development for positron emission tomography (PET) and single photon emission computed tomography (SPECT) has been dopamine and serotonin neurotransmission. This chapter reviews the PET and SPECT neurochemical brain imaging studies to understand the neurochemical mechanisms underling depression and the response to treatment. It examines the clinical and methodological aspects involved in the design, analysis and interpretation of neurochemical imaging studies. The chapter overviews the studies on neurochemical imaging in depressive illness. While the majority of studies have focused on unipolar depression, the chapter discusses the available data on other depression subtypes. The serotonin and dopamine systems have been the major focus of in-vivo neurochemical imaging studies in depression, as well as other conditions including schizophrenia and anxiety disorders. The chapter also reviews the available neurochemical imaging data for other neurotransmitter systems, and highlights active areas of radiotracer development for other potentially important neurochemical targets.
  • 12 - Neuroimaging of mood disorders: commentary
    pp 197-204
    • By Paul E. Holtzheimer III, Department of Psychiatry and Behavioral Sciences Emory University School of Medicine Atlanta, GA, USA, Helen S. Mayberg, Department of Psychiatry and Behavioral Sciences Emory University School of Medicine Atlanta, GA, USA
  • View abstract

    Summary

    The field of mood disorders neuroimaging is vibrant, productive and at times chaotic. This chapter first addresses the clear variance between structural and functional neuroimaging study findings of depression and bipolar disorder. When reviewing the mood disorders neuroimaging literature to date, one can appreciate a consistent set of brain regions (including gray and white matter components) as critical to normal and abnormal mood regulation. The consistency across imaging studies in location of abnormality, if not always direction, provides a useful starting point for future investigation. The chapter suggests two primary goals for a mood disorders imaging research agenda: increasing the signal-to-noise ratio for structural and functional imaging studies through technological developments, large-scale multi-center trials and novel analytic methods; and shifting from hypothesis-free to hypothesis-guided investigations based within developing neural network models. It is expected that neuroimaging findings will be able to play a vital role in diagnosis, and treatment development.
  • Section III - Anxiety Disorders
  • View abstract

    Summary

    Post-traumatic stress disorder (PTSD) includes a constellation of disabling behavioral and emotional symptoms that occur in a proportion of individuals exposed to severe psychological trauma. This chapter reviews the structural neuroimaging findings pertaining to specific brain regions in adults with PTSD. Although the majority of adult neuroimaging reports have centered on the hippocampus, medial prefrontal cortex, and amygdala, structural studies are potential abnormalities in other brain regions as well. The cavum septum pelucidum (CSP), a small cerebrospinal fluid filled cleft in the anterior portion of the septo-callosal junction, has been found to exist with greater frequency in individuals diagnosed with PTSD. Pediatric studies of PTSD have not fully replicated findings reported in the adult literature, and suggest that the neuroanatomical correlates of PTSD may manifest in a more generalized manner in children and adolescents who are traumatized.
  • 14 - Functional imaging of post-traumatic stress disorder
    pp 214-228
    • By Lisa M. Shin, Department of Psychology Tufts University Medford, MA, USA and Department of Psychiatry Massachusetts General Hospital Harvard Medical School Boston, MA, USA, Kathryn Handwerger Brohawn, Department of Psychology Tufts University Medford, MA, USA, Danielle L. Pfaff, Department of Psychology Tufts University Medford, MA, USA, Roger K. Pitman, Department of Psychiatry Massachusetts General Hospital Harvard Medical School Boston, MA, USA
  • View abstract

    Summary

    Post-traumatic stress disorder (PTSD) is an anxiety disorder that can develop in individuals who are exposed to an event or events that involve the threat of death or serious injury, and react with intense fear, helplessness or horror. This chapter summarizes a neurocircuitry model of PTSD and briefly describes the techniques that have been used to study brain function in this disorder. Researchers studying brain function in PTSD have implemented a wide variety of imaging techniques, including positron emission tomography (PET), single photon emission computed tomography (SPECT), and functional magnetic resonance imaging (fMRI). The chapter presents the results of functional neuroimaging studies that have yielded findings relevant to the amygdala, medial prefrontal cortex, and hippocampus in PTSD. It organizes the studies according to both the type of stimuli and the type of imaging technique used.
  • 15 - Molecular imaging of post-traumatic stress disorder
    pp 229-235
    • By J. Douglas Bremner, Department of Psychiatry and Department of Radiology Emory University School of Medicine Atlanta, GA, USA
  • View abstract

    Summary

    Recent advances in brain imaging have permitted an examination of alterations in brain function in patients with post-traumatic stress disorder (PTSD). This chapter reviews findings from neuro-chemical and neuroreceptor brain imaging measured with positron emission tomography (PET), single photon emission computed tomography (SPECT) and magnetic resonance spectroscopy (MRS). Neurochemical brain systems involved in the stress response are also affected by PTSD. These include norepinephrine, the hypothalamic-pituitary-adrenal (HPA) axis, serotonin, opiate and benzodiazepine systems. Using magnetic resonance imaging (MRI), it is possible to measure the physical properties, or spectra, of individual chemicals in the brain. Brain imaging studies are consistent with dysfunction of the hippocampus and anterior cingulate in PTSD. Several studies have looked specifically at neurochemical alterations in the hippocampus, and some have also looked at the anterior cingulate, most using N-acetyl-aspartate (NAA) as a marker of neuronal integrity.
  • 16 - Structural imaging of obsessive–compulsive disorder
    pp 236-246
    • By Andrew R. Gilbert, Department of Psychiatry University of Pittsburgh School of Medicine Pittsburgh, PA, USA, Alison M. Gilbert, Department of Psychiatry University of Pittsburgh School of Medicine Pittsburgh, PA, USA, Jorge R. C. de Almeida, Department of Psychiatry University of Pittsburgh School of Medicine Pittsburgh, PA, USA, Philip R. Szeszko, Department of Psychiatry The Zucker Hillside Hospital Glen Oaks, NY, USA and Albert Einstein College of Medicine Bronx, NY, USA
  • View abstract

    Summary

    This chapter presents findings from structural neuroimaging studies of obsessive-compulsive disorder (OCD) in both pediatric and adult populations. It reviews the structural neuroimaging literature with a focus on regions strongly implicated in the pathophysiology of OCD, including the orbitofrontal cortex, anterior cingulate cortex, basal ganglia, and thalamus. Structural neuroimaging studies have identified abnormalities in CST neural systems, especially in the orbitofrontal cortex and have informed many of the dominant neurobiological models of OCD. The emergence of magnetic resonance (MR) imaging techniques advanced the field by providing higher-resolution images without the potential risk of ionizing radiation. Several structural neuroimaging studies reported less gray matter in the amygdala and hippocampus in adult patients with OCD compared to healthy controls, although Kwon et al. reported larger amygdala volume in patients. Recently, investigators have used diffusion tensor imaging (DTI) to investigate the potential role of white matter abnormalities in the pathogenesis of OCD.
  • 17 - Functional imaging of obsessive–compulsive disorder
    pp 247-259
    • By Bon-Mi Gu, Interdisciplinary Program in Brain Science Seoul National University College of Medicine Seoul, Korea, Do-Hyung Kang, Department of Psychiatry Seoul National University College of Medicine Seoul, Korea, Jun Soo Kwon, Interdisciplinary Program in Brain Science and Department of Psychiatry Seoul National University College of Medicine Seoul, Korea
  • View abstract

    Summary

    Functional magnetic resonance imaging (fMRI) research in obsessive-compulsive disorder (OCD) has explored a broad range of cognitive functions, in addition to the neural correlates of symptom provocation and symptom improvement after treatment. There are some discrepancies between findings of symptom provocation fMRI research, which might be caused by the heterogeneous character of OCD, such as the variety of the symptoms and comorbidity, or the diversity of applied cognitive paradigms in neuroimaging research. Future research on symptom-specific neural correlates and related cognitive dysfunctions will bring better understanding to the pathophysiology of OCD. In addition, genetic or family studies will give information regarding traits or state-related characteristics as well as putative vulnerabilities to the disorder. Finally, considering the current model of cortico basal ganglia-thalamo-cortical loop dysfunction of OCD, functional connectivity research that examines the functional relationships between these brain areas will facilitate the understanding of the disorder.
  • 18 - Molecular imaging of obsessive–compulsive disorder
    pp 260-273
    • By Martijn Figee, Department of Psychiatry University of Amsterdam Amsterdam, The Netherlands, Jan Booij, Department of Nuclear Medicine University of Amsterdam Amsterdam, The Netherlands, Damiaan Denys, Department of Psychiatry University of Amsterdam Amsterdam, The Netherlands
  • View abstract

    Summary

    Functional imaging studies indicate involvement of the cortico-striatal-thalamic-cortical circuit in Obsessive-compulsive disorder (OCD) pathophysiology. This chapter reviews positron emission tomography (PET) and single photon emission computed tomography (SPECT) binding studies on serotonin and dopamine, and all available 1H magnetic resonance spectroscopy (1H MRS) research into glutamate levels in OCD. It combines these findings into a pathophysiological model for dysfunctional neurotransmission in OCD. Eight studies have investigated serotonergic neurotransmission in OCD, by comparing the availability of serotonin transporter (SERT) or 5-HT2a receptors between patients and healthy controls. Five studies used 1H MRS to estimate brain levels of glutamate in OCD patients and healthy controls, including one study that performed measures before and after serotonin reuptake inhibitors (SRI) treatment. Results from SPECT and PET binding studies suggest that OCD is related to decreased presynaptic SERT availability in thalamic and midbrain-pons regions, along with increased post-synaptic 5-HT2a receptor availability in cortical areas.
  • 19 - Structural imaging of other anxiety disorders
    pp 274-287
  • View abstract

    Summary

    Neuroimaging techniques permit the invivo evaluation of the human brain, allowing a better understanding of its anatomical, functional and metabolic substrate. This chapter reviews the literature which uses MRI for morphometric evaluation of the brain in studies related to anxiety disorders, with an emphasis on panic disorder (PD), generalized anxiety disorder (GAD), social anxiety disorder (SAD), and simple phobias. The neurobiology of GAD seems to involve neurochemical, neuroendocrine, neurophysiological, and genetic factors. Recent functional neuroimaging studies in patients with SAD suggest that the medial and orbito-prefrontal areas may be involved in the physiopathology of the disorder. Structural neuroimaging studies of GAD are still in an early phase. The studies reviewed in the chapter involve highly heterogeneous samples, reflecting the methodological difficulties in conducting studies of this disorder in samples with a precise diagnosis and with no comorbidities.
  • 20 - Functional imaging of other anxiety disorders
    pp 288-294
    • By Oliver Tüscher, Department of Radiology and Imaging Sciences Indiana University School of Medicine Indianapolis, IN, USA, Daniel J. Zimmerman, Department of Neurology andDepartment of Psychiatry and PsychotherapyUniversity of FreiburgFreiburg, Germany, David A. Silbersweig, Department of Psychiatry Brigham and Women's Hospital Harvard Medical School Boston, MA, USA
  • View abstract

    Summary

    Structural and functional neuroimaging studies have contributed enormously to the understanding of the neural substrates of panic disorders (PD). Functional magnetic resonance imaging (FMRI) studies have highlighted the importance of amygdala, anterior cingulate (ACC) and prefrontal cortex dysfunction in the pathophysiology of PD, features shared by other anxiety disorders. To further discern unique PD-related neural dysfunction in comparison to another major anxiety disorder, and to probe the neural substrates of this fear network, the authors have recently applied an instructed fear paradigm consisting of a Threat and a Safe condition to PD, Posttraumatic stress disorder (PTSD) and healthy subjects. Recent models have proposed a neuronal fear network with the amygdala at its center which is controlled by medial prefrontal areas and the hippocampus. In this model, amygdala projections to brainstem nuclei might trigger many of the somatic anxiety symptoms during a panic attack.
  • 21 - Molecular imaging of other anxiety disorders
    pp 295-307
    • By James W. Murrough, Department of Psychiatry Mount Sinai School of Medicine New York, NY, USA, Sanjay J. Mathew, Department of Psychiatry and Behavioral Sciences Baylor College of Medicine Houston, TX, USA
  • View abstract

    Summary

    This chapter reviews the neurochemical imaging literature in the anxiety disorders, focusing on key findings in post-traumatic stress disorder (PTSD), panic disorder (PD), social anxiety disorder (SAD) and generalized anxiety disorder (GAD). It provides a partial review of preclinical and human investigations of several neurochemical systems relevant to neurochemical imaging of anxiety disorders: namely the 5-HT, gamma-aminobutyric acid-benzodiazepine (GABA-BZD) and dopamine (DA) systems. Genetic analyses of polymorphisms of the major DA metabolizing enzyme catechol-O-methyltransferase (COMT) have suggested an association between specific polymorphisms and anxiety disorders, although these findings await replication. Several studies have utilized 1H-magnetic resonance spectroscopy (MRS) to investigate potential abnormalities in N-acetyl-aspartate (NAA), choline (CHO), creatine (CR) or lactate in GAD. As anxiety disorders are frequently comorbid with mood disorders, investigations of patients with anxious depression may be informative in determining specificity of neurochemical abnormalities.
  • 22 - Neuroimaging of anxiety disorders: commentary
    pp 308-312
    • By Scott L. Rauch, Department of Psychiatry McLean Hospital Harvard Medical School Belmont, MA, USA
  • View abstract

    Summary

    This chapter highlights the diagnosis, pathophysiology, etiology, and clinical utility, as well as trends in the evolution of psychiatric neuroimaging of anxiety disorders such as post-traumatic stress disorder and obsessive-compulsive disorder. Over the past 20 years, the authors have seen a movement toward studies of much larger cohorts of subjects, which helps to mitigate risks of statistical error, by providing greater statistical power and potentially more representative samples. There is a movement toward multi-modal imaging, where data gathered across various methods can bring together structural, functional, and chemical indices to provide greater depth, texture, and convergent validity to findings. Likewise, assessment of inter-regional correlations, and methods that enable finer temporal resolution, reflect greater sophistication in assessing the brain basis of healthy functions as well as diseases and their treatments.
  • Section IV - Cognitive Disorders
  • View abstract

    Summary

    The computational anatomy techniques enable us to detect and to visualize discrete changes in cortical and hippocampal integrity and to track the spread of Alzheimer's disease (AD) pathology throughout the living brain. This chapter focuses on the new generation of cortical and hippocampal mapping techniques, while reviewing the research findings reported in the literature. The computational anatomy field is based on mathematical approaches for modeling anatomical structures in brain images. 3D surface-based analyses have documented the relentless progression of AD pathology-driven changes from pre-dementia of the Alzheimer's type (DAT) to moderate DAT. An important utility of the cortical mapping approaches is the exploration of brain-behavior correlations. For decades, DAT clinical trial design has relied solely on cognitive and functional outcome measures. A major advantage of computational anatomy techniques is to track the disease process in 3D, revealing the dynamic sequence in which brain structures are affected.

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