bluuebunny/crossref_metadata_2025 huggingface dataset:
Genetics of Anxiety Disorders
Authors: Perez Javier A. , Otowa Takeshi , Roberson-Nay Roxann , Hettema John M.
Published: February 2014

This chapter provides a broad overview of the state of current research in the genetics of the major anxiety disorders. In addition tosummarizing findings regarding the individual clinical syndromes, we present data supporting genetic hypotheses that explain their comorbidity with each other and with related phenotypessuch as anxious personality traits and depression. We conceptually divide the chapter into three main sections based upon methodology: (1) genetic epidemiology of adult and pediatric anxiety (twin and family studies), (2) human molecular genetics (linkage and association), and (3) animal genetic models. These approaches provide complimentary and concurring evidence supporting the genetic basis underlying anxiety disorders as well as preliminary insight into the genetic mechanisms involved in their expression.
Prefrontal Cortex Regulation of Emotion and Anxiety
Authors: Graham Bronwyn M. , Milad Mohammed R.
Published: February 2014

The ability to appropriately regulate fear and anxiety is considered a top-down process involving higher-level cortical structures. Here, we review evidence that the prefrontal cortex (PFC) is critically involved in many laboratory emotion regulation tasks in both rodents and humans, including behavioral or experiential forms of regulation like fear extinction, and cognitive forms of regulation like reappraisal. We also discuss research demonstrating that failures in emotion regulation, as observed in many psychiatric conditions like anxiety disorders, are associated with PFC structural abnormalities and/or aberrant PFC functional activity. We conclude that the PFC may act as a common gateway between higher-level cortical structures and limbic/brainstem areas to mediate the appropriate control of emotions, irrespective of the regulation strategy (i.e., behavioral or cognitive) employed.
Developmental Components of Fear and Anxiety in Animal Models
Authors: Pattwell Siobhan S. , Mouly Anne-Marie , Sullivan Regina M. , Lee Francis S.
Published: February 2014

Fear learning is an adaptive, evolutionarily conserved process that allows one to respond appropriately to threats within the environment. In the case of psychiatric disorders, however, fear may persist long after an environmental threat has passed. This unremitting and often debilitating form of fear is a core component of many anxiety disorders, including post-traumatic stress disorder (PTSD), and involves exaggerated and inappropriate fear responses. The normative developmental trajectory of fear responsiveness is continually modified and sculpted throughout ontogeny to fit the dynamic needs of an organism across the lifespan. In this chapter, we review neural circuitry implicated in fear learning and present data from rodent and human fear learning studies spanning infancy to adulthood. In addition, we propose a developmental model of fear neural circuitry that may optimize current treatments and inform when, during development, specific treatments for anxiety may be most effective.
Functional Neurocircuitry and Neuroimaging Studies of Anxiety Disorders
Authors: Goodkind Madeleine S. , Gyurak Anett , Etkin Amit
Published: February 2014

Anxiety and fear serve adaptive functions and include wide-ranging subjective, physiological, behavioral, and cognitive responses. When these reactions are present chronically, and to a heightened degree that generalizes to signals beyond those that are objectively dangerous, one sees emergence of clinical anxiety disorders. Historically, anxiety disorders have been conceptualized as disruptions in fear processing, though more recent accounts also highlight changes in emotional reactivity beyond fear and deficits in emotion regulation. In this chapter, we review the neural circuitry relevant for fear processing and for emotional reactivity and regulation more broadly. We then review neuroimaging studies of social anxiety disorder, specific phobia, generalized anxiety disorder, panic disorder, and posttraumatic stress disorder. We highlight areas of overlap between disorders as well as disorder-specific perturbations.
Novel Treatment Approaches for Anxiety Disorders
Authors: Van Zwieten Anita , Alvares Gail A. , Guastella Adam J.
Published: February 2014

This chapter discusses novel pharmacological and cognitive approaches in the treatment of anxiety disorders. In particular, evidence is reviewed for glucocorticoids, yohimbine chloride, and D-cycloserine (DCS) as pharmacological adjuncts that augment fear extinction processes in psychotherapy, as well as cognitive bias modification (CBM) programs designed to remediate biased cognitive processes. These treatment approaches aim to capitalize on the cognitive, neurobiological, and behavioral mechanisms that underlie anxiety disorders. Novel technological approaches that aim to enhance access to anxiety treatment are also reviewed, specifically in reference to internet- and computer-based psychotherapy (ICT). Along with their proposed mechanisms of action, empirical evidence for their efficacy, acceptability, and cost-effectiveness are explored, as well as directions for future research.
Pharmacotherapy of Anxiety Disorders
Authors: Murrough James W. , Iosifescu Dan V. , Charney Dennis S.
Published: February 2014

Anxiety disorders are among the most prevalent mental disorders in the United States and are associated with a high degree of morbidity and public health costs. This chapter will present a general approach to the diagnosis and treatment of these disorders and summarize the current evidence base for pharmacotherapeutic treatment options in individual disorders, including panic disorder, social phobia, posttraumatic stress disorder, generalized anxiety disorder.The serotonin-selective and serotonin norepinephrine reuptake inhibitors are generally considered first-line treatment while older monoaminergic agents are often efficacious but are limited by safety and tolerability issues. The benzodiazepines play an important role in the treatment of some anxiety disorders, however these agents also possess important limitations. Other pharmacological agents have a more limited evidence base. Continued progress in basic and translational neuroscience is expected to meet the need for new, more effective treatments for patients suffering from these disorders.
Neurobiology and Treatment of OCD
Authors: Ahmari Susanne E. , Simpson H. Blair
Published: February 2014

Obsessive Compulsive Disorder (OCD) is a chronic, disabling disorder with a lifetime prevalence of up to 2-3%, and is a leading cause of illness-related disability. OCD is characterized by recurrent intrusive thoughts, images, or impulses (obsessions) that cause anxiety or distress, and repetitive mental or behavioral acts (compulsions). Though the etiology of OCD is unclear, current evidence implicates both genetic and environmental factors in its development. Our understanding of the neurobiology underlying OCD is still evolving, with convergent evidence from clinical and preclinical studies highlighting the importance of abnormalities in cortico-striatal-thalamo-cortical (CSTC) circuits. Evidence-based treatments for OCD include both pharmacotherapy and cognitive-behavioral therapy. This chapter will review the etiology and neurobiology of OCD, and will provide an overview of treatment strategies.
Animal Models of Addiction
Authors: Maldonado Rafael , Jentsch J. David , Kieffer Brigitte L. , Evans Christopher J.
Published: February 2014

Drug addiction is a chronic brain disease considered to result from a series of transitions from voluntary use in search of a hedonic effect, to loss of control over this behavior, and ultimately to compulsive behavior. Important in the context of mental illness is that substance use disorders are comorbid with many psychiatric diseases, including depression, anxiety and schizophrenia. In current research on addiction, animal models recapitulate the phenotypes contributing to abuse susceptibility through initial drug taking, habitual drug taking, abstinence and finally relapse. These models have begun to unravel the molecular, cellular, and behavioral adaptations regulating addictive behaviors in research which has greatly enriched our understanding of the neurocircuitry mediating learning, motivation, mood and stress. This chapter systematically explores animal models that contribute insights to addiction behaviors including, reward, reinforcement, abstinence, relapse, and susceptibility for initiating additive behaviors.
Cellular and Molecular Mechanisms of Addiction
Authors: Reissner Kathryn J. , Kalivas Peter W.
Published: February 2014

Exposure to drugs of abuse is for most individuals a reinforcing experience which can lead to continued use and the development of an addiction disorder. Evidence indicates that the escalation in use and ultimately compulsive motivation to obtain drug is linked to long lasting cellular changes within the brain reward neurocircuitry. In this chapter we will describe the transition in use from isolated social use to habitual relapse, and within that context will describe the neurocircuitry implicated in this process and the enduring cellular and molecular changes which occur within that circuitry that may mediate preoccupation with drug seeking in the addiction vulnerable individual.
Molecular Imaging in Addictive Disorders
Authors: Robertson Chelsea L. , Berman Steven M. , London Edythe D.
Published: February 2014

Positron emission tomography (PET) and single photon emission computed tomography (SPECT) have helped reveal the neural circuits and transmitters involved in addiction. From vulnerability factors and acute pharmacological responses topersistent behavioral states that represent important therapeutic targets, PET and SPECT imaging have contributed to the delineation of several mechanisms by which substance dependence develops in humans. Commonalities across addictive disorders include dopaminergic deficits and corticolimbic dysfunction that can lead to imbalance between responses to imminent rewards and inhibitory control, promoting maladaptive behaviors. Despite progress, the field is limited by a need for additional neurochemical probes for relatively unexplored but relevant systems, such as those involving glutamate, kappa-opioid and cannabinoid receptors.
Magnetic Resonance Spectroscopy Studies in Substance Abusers
Authors: Chang Linda , Cloak Christine C. , Holt John L.
Published: February 2014

Brain metabolites reflecting neuronal and glial content can be measured with in vivomagnetic resonance spectroscopy (MRS),which has been applied to assess the brain health associated with various drugs of abuse. The specific neurochemical alterations associated withseveral major categories of abused drugs, including those from psychostimulants, inhalants, opiates, alcohol, and cannabis, were reviewed and compared. Sometechnical issues to be considered in the use of MRS to assess brain pathology and the future directions of MRS to assess drugs of abuse were also discussed.
Epidemiology of Substance Use Disorders
Authors: Kandel Denise B. , Hu Mei-Chen , Griesler Pamela C.
Published: February 2014

This chapter reviews the epidemiology of substance use, abuse and dependence on alcohol, nicotine and illicit drugs in the population among adults and adolescents; comorbidity with psychiatric disorders; the importance of early onset; and animal models of the Gateway Hypothesis. Existing epidemiological studies and reports have many limitations, necessitating extensive secondary analysis of the data sets to overcome some of those limitations. Nicotine is the most addictive of the drugs and the most chronic addiction. It is the one substance for which dependence is higher among women than men. Adolescence is a period of increased risk for drug abuse and dependence among last year users. Psychiatric comorbidity with substance use disorders is high, especially for antisocial personality disorder. Animal models of the Gateway Hypothesis have uncovered basic mechanisms of nicotine action in the brain.
Clinical and Neuropsychological Features of Alzheimer’s Disease
Authors: Hassenstab Jason , Burns Jeffrey , Morris John C.
Published: February 2014

This chapter reviews the clinical and neuropsychological characteristics and course of dementia caused by AD with a focus on its earliest symptomatic stages, as the typical person affected by AD is not profoundly demented (48% of individuals affected by AD are mildly demented, 31% are moderately demented, and only 21% are severely demented (Hebert et al., 2003)). The chapter is written from the viewpoint of the clinician. It addresses the variability in current sets of clinical diagnostic criteria for AD, and provides the rationale for the use of biological markers (biomarkers) to aid in moving the diagnostic process from a syndromic to a quantitative basis.
The Genetics of Alzheimer’s Disease
Authors: Tanzi Rudolph E.
Published: February 2014

Risk for Alzheimer’s disease (AD) is strongly influenced by genetics. In fact, following age, the second strongest risk factor for AD is family history. To date, genetic studies have thus far demonstrated that the inheritance of AD is dichotomous. Roughly half of the cases of the rare early-onset (<60 years) familial form of AD (EO-FAD) are caused by rare mutations in APP, PSEN1, and PSEN2.These mutations usually guarantee onset and account for ~5% of AD. The major gene influencing risk for late-onset AD (LOAD) is APOE. The ε‎4 and ε‎2 variants increase and decrease risk for AD, respectively. Together, these four genes account for up to 50% of the genetic variance of AD. To find the remaining AD genes, multiple genome-wide association studies (GWAS) have resulted in the identification of eleven other AD candidate genes. In this review, I summarize the current state of our knowledge of the genetic factors influencing risk for AD and prospects for future studies.
Structural, Functional, and Molecular Neuroimaging Biomarkers for Alzheimer’s Disease
Authors: Brewer James B. , Sepulcre Jorge , Johnson Keith A.
Published: February 2014

Advances in quantitative structural, functional, and molecular neuroimaging have provided new tools for objective, in vivo, assessment of critical aspects of Alzheimer’s disease and other neurodegenerative disorders. Measures of brain atrophy or brain dysfunction, coupled with measures of disease-linked pathology, might complement the history, physical and neurocognitive evaluation of patients and thereby improve predictive prognosis, especially at early stages of cognitive impairment where neurodegenerative etiology is less certain. Such imaging biomarkers are currently used in nearly all clinical trials of therapeutic agents for Alzheimer’s disease and are increasingly incorporated into clinical practice. In this chapter, imaging biomarkers are introduced and discussed to familiarize the reader with their potential research and clinical uses.
Fluid Biomarkers for Alzheimer’s Disease
Authors: Fagan Anne M.
Published: February 2014

Dementia due to Alzheimer’s disease (AD) is estimated to reach epidemic proportions by the year 2030. Given the limited accuracy of current clinical diagnosis, biomarkers of AD pathologies are being sought. Reductions in cerebrospinal fluid (CSF) levels of Aβ‎42 (marker of amyloid plaques) and elevations in tau species (markers of neurofibrillary tangles and/or neurodegeneration) are useful for AD diagnosis and prognosis. Novel CSF and plasma/serum biomarkers are being explored to aid in discriminating AD from non-AD neurodegenerative diseases andidentifying additional AD-related processes (e.g., neuroinflammation and early neuronal stress and dysfunction). Biomarkers are being considered for use in clinical trial design and inclusion in revised diagnostic criteria for research and clinical applications. Emphasis is on early (even ‘preclinical’) detection in order to identify and applytherapies that have the best chance of preserving normal cognitive function.
Clinical Features and Pathogenesis of Frontotemporal Dementia
Authors: Naasan Georges , Miller Bruce
Published: February 2014

Frontotemporal dementia describes a group of insidious and slowly progressive clinical syndromes that are due to frontal and/or temporal lobe dysfunction including a behavioral variant, a semantic variant, and a non-fluent aphasia variant. The diagnosis is reached through a careful, detailed history and a neurological and neuropsychological examination. Imaging techniques can help support the diagnosis and identify unique patterns of brain atrophy. Various underlying neuropathologies have been described and are related to protein misfolding implicating primarily tau or TAR DNA-binding protein 43. In its familial form, FTD can result from mutations in MAPT, PGRN, or C9orf72. Treatment currently focuses on a multidisciplinary approach involving patient and caregiver education, and social support through day care center and support groups. Pharmacological treatment is mainly symptomatic although disease-modifying therapies are being studied.
Pathogenesis, Diagnosis, and Treatment of Vascular and Mixed Dementias
Authors: Chui Helena Chang
Published: February 2014

This chapter addresses five common questions surrounding vascular cognitive impairment (VCI): pathogenesis, diagnostic accuracy, incidence and prevalence, relationship between VBI and Alzheimer disease (AD), and prevention/treatment. Although vascular cognitive impairment is considered to be the second most common form of cognitive impairment and dementia in late life, it can be argued that public health emphasis should be placed more on the prevention and treatment of vascular brain injury (VBI), which for example may be detectable by MR imaging. We review the historical syndromes and current diagnostic criteria, which have focused on defining various subtypes of VCI and have influenced estimates of incidence and prevalence. Recent neuropathological studies have highlighted the frequent concurrence of Alzheimer pathology and VBI in late life. Converging evidence suggests that AD and VBI impose differential but additive deleterious effects on cognitive function. The field is moving increasingly to earlier detection of the brain at risk using MR imaging, as well as to the early identification and treatment of vascular risk factors.
Clinical Features and Pathogenesis of Prion Disease
Authors: Watts Joel C. , Geschwind Michael D.
Published: February 2014

Prion diseases are uniformly fatal neurodegenerative diseases that typically are rapidly progressive. They are unique in the annals of medicine in that they occur in three ways: sporadic, genetic, and acquired. The reader might ask why prion diseases are included in a textbook on mental illness. As we will try to show in this chapter, psychiatric features are often an early and prominent feature of many prion diseases, although sometimes these features are overshadowed by the more obvious neurological, particularly cognitive and motor, features.

The most common form of human prion disease is called sporadic Jakob-Creutzfeldt disease (sCJD), which comprises about 85-90% of all human prion diseases, followed by genetic forms comprising about 10-15%, and lastly acquired forms, which although the most notorious, are the least common at less than 1% 1. Before discussing these different presentations of prion disease, we will present some historical background on prion diseases, including discussing relevant nomenclature.
Epigenetics in Early Life Programming
Authors: Bale Tracy L.
Published: February 2014

Fetal antecedents such as maternal stress, infection or dietary challenges have long been associated with an increased disease risk, capable of affecting multiple generations. The mechanisms through which such determinants contribute to disease development likely involve complex and dynamic relationships between the maternal environment, the endocrine placenta, and the epigenetic programming of the developing embryo itself. While an appreciation for the importance of the epigenome in offspring disease predisposition had evolved, the incredible variability in critical factors such as gestational timing of insults, sex of the fetus, and maternal genetics make clear interpretations difficult. However, animal models have proven highly informative in providing the best knowledge yet as to just how dynamically responsive the epigenome is, and in determining important mechanisms that shape and reprogram the developing brain. This chapter will discuss the epidemiological and clinical evidence and supportive animal models related to environmental influences on neurodevelopmental and neuropsychiatric disease risk.
Animal Models in Psychiatric Disorders of Childhood Onset
Authors: Paylor Richard , Thomas Alexia M. , Veeraragavan Surabi , Hamilton Shannon M.
Published: February 2014

Research to elucidate the mechanisms underlying psychiatric disorders can be challenging with regards to childhood disorders, in which human samples available to researchers are not only limited, but there are also ethical considerations regarding the ability of children to provide informed consent. Therefore animal models provide an alternative for studying the complex behavior associated with neurological and psychiatric disorders of childhood-onset. Behaviors in rodent models are likely not completely analogous to human behavior and the models must meet face validity, construct validity and predictive validity to be considered relevant. This chapter highlights the major animal models currently used in the research of childhood-onset psychiatric disorders.
Neuropathology and Synaptic Alterations in Neurodevelopmental Disorders
Authors: Dierssen Mara , Martínez Salvador
Published: February 2014

Neurodevelopmental disorders include a myriad of conditions, in which symptomatic presentation and disease onset is identifiable in early postnatal years, prior to full brain maturation. Both genetic and environmental insults can lead to neurodevelopmental disorders, which result from anatomical and physiological abnormalities during the development and maturation of brain circuits. Mental disorders become symptomatic in childhood or adolescence and are affected by early environmental conditions that may interact with genetic risk factors. Neurodevelopmental disorders share a number of similarities in terms of common genetic risks, co-occurrence of neurodevelopmental symptom domains, cognitive processing deficits, early onset and chronic course. Schizophrenia, autism and intellectual disabilities, for example, are spectrums of diseases with broad sets of causes that have overlapping phenotypes and genetics, which is suggestive of common deficits.
Intellectual Disability Syndromes
Authors: Schwartz Charles E. , Gurrieri Fiorella , Neri Giovanni
Published: February 2014

Intellectual disability (ID) constitutes a spectrum of chronic human diseases that occur in about 1-3% of the population. This spectrum includes those precipitated by environmental factors as well as genetic disorders, the latter including some that are relatively prevalent, such as Down syndrome and fragile X syndrome, to rather “private” conditions limited to a few individuals with small chromosomal duplications or deletions. With the assistance of tremendous advances in technology – chromosome microarray analysis and next generation sequencing – it is now possible to arrive at a genetic diagnosis in a significant proportion of individuals with such forms of ID. Clinical evaluation remains the most effective means by which a clinician can prioritize diagnostic approaches to pursue for an individual with ID. This chapter briefly describes the clinical aspects of selected ID syndromes, grouped by the mode of inheritance. The selection was done with the goal of illustrating better known as well as less well known molecular pathways and cellular compartments whose disruption results in ID in association with additional clinical features. These pathways and compartments represent important modules for study using neurobiological methods, and for improved neuronal and neural systems-level understanding of the biology of typical brain function and of the pathophysiology of mental illness.
Autism Spectrum Disorders
Authors: Kolevzon Alexander , Wang A. Ting , Grodberg David , Buxbaum Joseph D.
Published: February 2014

Autism spectrum disorders (ASD) manifest with deficits in social communication, together with the presence of repetitive behaviors and restricted interests.Behavioral interventions are important first-line treatments in ASD and there is a need for pharmacological treatments that target core symptoms of ASD. Neuroimaging studies implicate specific brain regions and networks in ASD, and there has beensignificant progress in identifying etiological genetic loci for ASD. Gene discovery, coupled with the development of animal model systems, have elucidated the neurobiology of several monogenic forms of ASD. These discoveries have in turn led to important opportunities for developing novel treatments and several clinical trials are underway with potentially disease-modifying medications that target core symptom domains. Although the state of the evidence is preliminary, these studies are the basis for enormous optimism in ASD and underscore how neurobiological approaches are likely to lead to novel therapeutics in ASD.
Tourette Syndrome and Tic Disorders
Authors: Williams Kyle , Bloch Michael H. , State Matthew W. , Pittenger Christopher
Published: February 2014

Tourette syndrome (TS), the most severe end of the spectrum of tic disorders, is characterized by episodic motor and vocal tics and attendant sensory phenomena. It is commonly comorbid with attention deficit disorder and obsessive-compulsive disorder. Functional imaging studies have implicated dysregulation of cortico-basal ganglia circuitry. TS is genetically complex; recent findings have identified several rare contributing mutations, and the heterogeneous genetic architecture of the condition is slowly coming into focus. Post-mortem findings have identified abnormalities of specific populations of interneurons that have led to new insight into the circuit-level disruptions of information processing that underlie this condition, though the etiology of interneuronaldysregulationremains unclear. Dysregulated immune-brain interactions, may contribute to a subset of cases. These varied sources of insight into the condition are gradually converging on informative models of tic disorder pathophysiology.
Novel Therapeutics in Childhood Onset Psychiatric Disorders
Authors: Grice Dorothy E. , Kolevzon Alexander , Kaufmann Walter E. , Buxbaum Joseph D.
Published: February 2014

Neurodevelopmental disorders are frequently the result of genetic and genomic abnormalities associated with high risk for disease. Creating analogous mutations in cell and animal models permits the assessment of underlying neurobiological mechanisms, generates clues about useful therapeutic targets, and provides systems for preclinical evaluation of novel therapeutics. This chapter briefly summarizes several clinical trials in neurodevelopmental disorders, all based on neurobiological findings in model systems, including trials in Down syndrome (DS) and several monogenic forms of intellectual disability (ID) and/or autism spectrum disorder (ASD).
DSM-5 Overview and Goals
Authors: Kupfer David J. , Schultz Susan K.
Published: February 2014

The road to DSM-5 spanned a decade of planning, discussion and review of the considerable advances in psychiatric research and clinical practice. By bridging the strengths of DSM-IV with the opportunities brought by new discoveries in neuroscience, the DSM-5 offers a foundation for future growth as we fill in our gaps of knowledge regarding the underlying pathologies of mental disorders. New features in DSM-5 include an organizational structure that permits alignment of disorders with shared putative pathogenesis irrespective of whether the disorders typically emerge in childhood or later in life. Other features include a new emphasis on risk factors and the development and life course of illness. The goal of the DSM-5 is to create a “living document” that may evolve over time as we gradually build on our knowledge of the neurobiologic underpinnings that account for both the emergence and lifetime expression of mental disorders.
Toward Precision Medicine in Psychiatry
Authors: Cuthbert Bruce N. , Insel Thomas R.
Published: February 2014

The brain is now commonly viewed as a complex information-processing system whose major circuits interact to implement effective behavior in motivational, cognitive, and regulatory domains. In turn, mental disorders are increasingly understood in terms of malfunctions in these systemsthat result from various combinations of genetic and environmental factors. The National Institute of Mental Healthy initiated the Research Domain Criteria project (RDoC) to support studies that caninform future versions of psychiatric nosologies based upon such empirically-derived dimensions of behavior and their implementing neural systems. This chapter describes the RDoC framework, and some of the theoretical and practical considerations that arise in devising an experimental approach to classification that can transcend current symptom-based diagnostic systems. We discuss examples of how such a long-term, translational effort could contribute toan empirically-based nosology that incorporates a precision medicine approach for assessment and treatment of mental disorders.
The Neurobiology of Personality Disorders: The Shift to DSM-5
Authors: Perez-Rodriguez M. Mercedes , New Antonia S. , Siever Larry J.
Published: February 2014

While neurobiologic studies are focused primarily on disorders that in DSM-IV were placed on Axis I, displaying extensive symptomatology and often in episodic fashion, there is an emerging neurobiology of personality disorders, which consists largely of maladaptive traits that impair functioning and adaptation to the environment. These constellations of maladaptive traits are partially heritable, associated with specific candidate genes that are beginning to be identified, and are grounded in specific neurocircuitry alterations. It is in part the recognition of the neurobiologic grounding of these disorders that has led to the placement of personality disorders onto Axis I in DSM-5.
The Neurobiology of Aggression
Authors: James R. , Blair R.
Published: February 2014

This chapter considers the neurobiology of aggression both the neural systems mediating this behavior as well as how these systems can become perturbed such that the aggression is maladaptive to the individual. A distinction will be drawn between planned, goal directed instrumental aggression and threat/ frustration based reactive aggression. Instrumental aggression implicates the neural systems involved in instrumental motor behavior generally as well as emotional learning and decision making systems that allow the selection of one action over another. Conditions decreasing the responsiveness of neural systems allowing good decision making (amygdala, striatum, ventromedial prefrontal cortex) are associated with an increased risk for maladaptive instrumental aggression. Reactive aggression implicates sub cortical systems involved in the basic response to threat as well as cortical systems involved in emotional modulation and the response to norm violations.
The Neurobiology of Social Attachment
Authors: Smith Adam S. , Lei Kelly , Wang Zuoxin
Published: February 2014

Social attachment is an intrinsic component of human life. As Aristotle famously noted, “man is by nature a social animal”, and as such, social attachments are wellsprings for our survival, success, and mental health. This dynamic process – involving complex behaviors, multimodal sensory information, and cognitive processes – leads infants to bond to their caregivers or two people to fall in love. Now, the neurobiological basis of attachment is coming to light, illuminating the role of various monoamines and neuropeptides. It is the goal of this chapter to describe the current knowledge of the neurobiology behind social attachments by uncoupling the neurochemical and neuroanatomy of individual bond-related behaviors, reconstructing uniformed neural systems, and correlating these findings to our understanding of human analogs.
The Neurobiology of Sleep
Authors: Tononi Giulio , Cirelli Chiara
Published: February 2014

Sleep is a state of reduced responsiveness to environmental stimuli, usually associated with immobility and stereotyped postures. It is universal and tightly regulated, suggesting that it is likely to serve some essential function. However, that function remains unclear. In this chapter we examine how sleep is traditionally subdivided into different stages that alternate in the course of the night, discuss the brain areas that determine whether we are asleep or awake, and summarize the negative consequences of sleep deprivation. We then discuss how brain activity changes between sleep and wakefulness and consider how this leads to the characteristic modifications of consciousness experienced during dreaming and dreamless sleep. Finally, we turn to the paramount but still mysterious question of sleep function.
The Neurobiology of Resilience
Authors: Feder Adriana , Haglund Margaret , Wu Gang , Southwick Steven M. , Charney Dennis S.
Published: February 2014

Resilience is the ability to adapt successfully to severe or chronic stress. Identifying the factors that set resilient individuals apart from those who are vulnerable to the effects of stress has clinical significance: understanding the neurobiology and psychology of resilience enables researchers and clinicians to develop new therapies for the prevention and treatment of stress-induced psychopathology in non-resilient individuals. This chapter outlines the current understanding of resilience, from genetic, epigenetic, developmental, psychological, and neurobiological perspectives, and promotes promising new therapies for the promotion of resilience to stress.
The Neurobiology of Eating Disorders
Authors: Hildebrandt Thomas B. , Downey Amanda
Published: February 2014

Eating disorders are recognized by a primary dysregulation in the ability to eat and the inability to maintain a healthy weight without significant and impairing levels of distress. Commonly beginning in adolescence and affecting primarily females, these illnesses have debated diagnostic criteria but retain core features including disturbances in the maintenance of a healthy weight, episodic binge eating and/or compensatory behaviors, and body image disturbances. The pathogenesis of eating disorders is not well understood, having historically been attributed to primarily sociocultural pressures to be thin. The dearth of effective interventions for eating disorders may stem from the lack of understanding of the complex neurobiological processes that contribute to the psychopathology of these illnesses. This chapter will provide a summary of the current research of the genetic, hormonal, neurotransmitter, and functional neurocircuitry of eating disorders. Dysregulation in appetite hormones and peptides, adrenal hormones, ovarian hormones, the serotonergic and dopaminergic systems and several central nervous system neurocircuits all show strong correlation to the development and maintenance of these chronic and frequently relapsing disorders. Future directions for laboratory, clinical, and translational research are discussed.
Introduction to the Electrophysiology Manual: Fluoroscopic Views, Electrograms, and Relevant Anatomy
Authors: Asirvatham Samuel J.
Published: February 2014

The purpose of this chapter is to familiarize the reader with the typical fluoroscopic views and electrograms used throughout this book. First, the rationale for the particular views used and the standard electrogram display format are introduced. The discussion then continues to the important fluoroscopic landmarks relevant to the arrhythmias encountered in the electrophysiology laboratory. These landmarks are discussed in the context of the electrograms obtained from mapping these sites and their importance from an anatomic and ablation standpoint. The first topics are the common fluoroscopic and anatomic principles relevant to the electrophysiology laboratory; then the specific differences in catheter use and electrograms obtained from the standard fluoroscopic catheter position in supraventricular tachycardia, atrial flutter, atrial fibrillation, and ventricular tachycardia; and finally some unusual positions and congenital variants.
Use of Intracardiac Echocardiography in Cardiac Electrophysiology
Authors: Friedman Paul A. , Asirvatham Samuel J.
Published: February 2014

Intracardiac echocardiography is increasingly used during invasive electrophysiology procedures. Common applications include guiding transseptal puncture, assessing potential complications, and identifying structures invisible under fluoroscopy. It is important to distinguish intravascular ultrasound from intracardiac ultrasound. Intravascular ultrasound uses high-frequency transducers that provide excellent high-resolution images but have limited tissue penetration. Intracardiac imaging uses lower frequencies, increasing tissue penetration to 14 cm and permitting “whole heart” imaging. The purpose of this brief introduction is to provide practical points of reference for use of intracardiac echocardiography and orientation to the images that follow in the remainder of the book. Thus, only images from the phased-array system are included.
Electroanatomic Mapping for Catheter Ablation of Cardiac Arrhythmias
Authors: Noheria Amit , Buescher Traci L. , Asirvatham Samuel J.
Published: February 2014

Examples of the use of 3 dimensional mapping systems are found throughout the detailed discussion of instructive arrhythmia cases in this text. Although the systems provide a powerful tool to better treat complex arrhythmia, the student of electrophysiology should be aware of the various pitfalls that sometimes result in confusion and inaccuracy with interpretation. The examples in this chapter give a basic appreciation of how the technology is used in arrhythmia management. The case discussions that follow include the specific utilities and pitfalls to avoid during application of these technologies.
Diagnostic Maneuvers Commonly Used in the Electrophysiology Laboratory: Understanding the Rationale, Techniques, and Interpretation
Authors: Asirvatham Samuel J.
Published: February 2014

Among the keys to successful ablation are the correct interpretation and thorough understanding of maneuvers commonly applied in the electrophysiology laboratory. Throughout this textbook, these maneuvers appear integrated in cases and in several of the other chapters. This chapter focuses on the maneuvers themselves rather than their particular applications in given cases. The rationale for each maneuver is described in some detail to allow the reader to anticipate and fully understand situations where the results from these maneuvers can be universally applied and to recognize exceptional circumstances. It should be apparent, after going through this chapter, that no single maneuver can be relied on to be diagnostic of a particular arrhythmia or solely used to guide ablation.
Approach to Wide QRS Tachycardias
Authors: Cha Yong-Mei , Asirvatham Samuel J.
Published: February 2014

Among the most difficult set of arrhythmias to analyze, diagnose, and treat appropriately in the electrophysiology laboratory are wide QRS tachycardias. The reasons for this difficulty include the relatively rare occurrence of some of these conditions and the fact that the differential diagnosis for a wide QRS rhythm includes all the possibilities for a narrow QRS rhythm and, in addition, arrhythmias related to antegrade pathway conduction and ventricular tachycardia. This wide range of possibilities can be confusing even to experienced electrophysiologists, and a complex case may lead to inappropriate diagnoses and maneuvers, including a wrong ablation sequence. This chapter focuses on the overall approach to wide QRS tachycardias. A brief description of the clinical and electrocardiographic features is followed by an in-depth discussion of diagnostic maneuvers and approaches in the electrophysiology laboratory. Finally, representative electrograms and case studies follow to illustrate some of the more involved principles discussed in this chapter.
Basic Cardiac Electrophysiology
Authors: Lee Hon-Chi , Jahangir Arshad
Published: February 2014

The learning objectives of this chapter are to review some basic electrophysiologic concepts that are useful for the clinician. These include 1) the structure and function of cardiac ion channels; 2) the role of ion channels in the generation of cardiac action potentials; 3) the mechanisms of cardiac arrhythmias; and 4) inherited and acquired channelopathies.
Antiarrhythmic Drug Therapy: Understanding Options for the Ablationist
Authors: Jahangir Arshad
Published: February 2014

Antiarrhythmic agents play an important role in the management of cardiac arrhythmias as both primary and hybrid therapy. The essential goals of antiarrhythmic therapy are termination of an ongoing arrhythmia, prevention of arrhythmia recurrence, or both. Antiarrhythmic drugs help control arrhythmias but also may cause them. Therefore, selection of an effective yet safe medication may be challenging. The challenge arises from factors intrinsic to the patient, the disease condition, or the drug itself. These factors include variability in the pathophysiologic substrate, arrhythmia mechanisms, clinical presentation, prognostic implications, drug disposition, and response. Patients with arrhythmia comprise a highly heterogeneous patient population, with variable comorbid conditions and concomitant drug use.
Glossary of Catheter Names
Authors: Asirvatham Samuel J. , Cha Yong-Mei , Friedman Paul A.
Published: February 2014

AA 1, to 19,20,

ascending aorta distal-proximal

ABL dis/prox (ABL d/p),

ablation distal/proximal

Aort Abl p,

aortic ablation catheter, proximal

CS 1, to 19,20,

coronary sinus distal-proximal

Epi 1, to 3,4,

epicardial catheter

Epi Uni,

epicardial unipolar

HBE 1–4,

His bundle electrogram distal-proximal

HIS dist/prox,...
Case 3
Authors: Asirvatham Samuel J. , Cha Yong-Mei , Friedman Paul A.
Published: February 2014

Case presentations focus on mapping techniques, diagnosis, and proper catheter placement for successful ablation of arrhythmias. This case focuses on wide QRS tachycardia, atrial activation, and near-field and far-field potentials.
Case 4
Authors: Asirvatham Samuel J. , Cha Yong-Mei , Friedman Paul A.
Published: February 2014

Case presentations focus on mapping techniques, diagnosis, and proper catheter placement for successful ablation of arrhythmias. This case focuses on atrial fibrillation treated with ablation.
Case 5
Authors: Asirvatham Samuel J. , Cha Yong-Mei , Friedman Paul A.
Published: February 2014

Case presentations focus on mapping techniques, diagnosis, and proper catheter placement for successful ablation of arrhythmias. This case focuses on sudden-onset, sudden-offset palpitations and AV node reentry.
Case 7
Authors: Asirvatham Samuel J. , Cha Yong-Mei , Friedman Paul A.
Published: February 2014

Case presentations focus on mapping techniques, diagnosis, and proper catheter placement for successful ablation of arrhythmias. This case focuses on ventricular extrastimulation testing, failure to sense, Brugada syndrome, and sudden unexplained death syndrome.
Case 8
Authors: Asirvatham Samuel J. , Cha Yong-Mei , Friedman Paul A.
Published: February 2014

Case presentations focus on mapping techniques, diagnosis, and proper catheter placement for successful ablation of arrhythmias. This chapter focuses on bundle branch block, accessory bypass tract, and preexcitation.
Case 9
Authors: Asirvatham Samuel J. , Cha Yong-Mei , Friedman Paul A.
Published: February 2014

Case presentations focus on mapping techniques, diagnosis, and proper catheter placement for successful ablation of arrhythmias. This case focuses on microbubbles on imaging, intracardiac ultrasonography, thrombi, and vessel perforation and dissection.
Case 10
Authors: Asirvatham Samuel J. , Cha Yong-Mei , Friedman Paul A.
Published: February 2014

Case presentations focus on mapping techniques, diagnosis, and proper catheter placement for successful ablation of arrhythmias. This case focuses on premature atrial contractions, tachycardia, atrial fibrillation, atrial flutter, and ectopy.
Case 12
Authors: Asirvatham Samuel J. , Cha Yong-Mei , Friedman Paul A.
Published: February 2014

Case presentations focus on mapping techniques, diagnosis, and proper catheter placement for successful ablation of arrhythmias. This case focuses on atrioventricular node reentrant tachycardia, junctional tachycardia, short-interval tachycardia, and parahisian pacing.
Case 15
Authors: Asirvatham Samuel J. , Cha Yong-Mei , Friedman Paul A.
Published: February 2014

Case presentations focus on mapping techniques, diagnosis, and proper catheter placement for successful ablation of arrhythmias. This case focuses on the adult with a history of congenital heart disease, tachypalpitations, atrial fibrillation, and atrial flutter.
Case 16
Authors: Asirvatham Samuel J. , Cha Yong-Mei , Friedman Paul A.
Published: February 2014

Case presentations focus on mapping techniques, diagnosis, and proper catheter placement for successful ablation of arrhythmias. This case focuses on atrial flutter, atrial fibrillation, the cavotricuspid isthmus, and intracardiac ultrasonography.
Case 17
Authors: Asirvatham Samuel J. , Cha Yong-Mei , Friedman Paul A.
Published: February 2014

Case presentations focus on mapping techniques, diagnosis, and proper catheter placement for successful ablation of arrhythmias. This case focuses on intractable atrial fibrillation, multiple atrial flutters, bilateral conduction block, accessory pathway conduction, junctional tachycardia, premature atrial contractions, H-A interval, H-H interval, H-V interval, A-H interval, and heart block.
Case 19
Authors: Asirvatham Samuel J. , Cha Yong-Mei , Friedman Paul A.
Published: February 2014

Case presentations focus on mapping techniques, diagnosis, and proper catheter placement for successful ablation of arrhythmias. This case focuses on incessant atrial tachycardia, ablative therapy, premature ventricular contraction, and isolation procedures.
Case 20
Authors: Asirvatham Samuel J. , Cha Yong-Mei , Friedman Paul A.
Published: February 2014

Case presentations focus on mapping techniques, diagnosis, and proper catheter placement for successful ablation of arrhythmias. This case focuses on “the difficult case.” Difficulties in diagnosis and treatment can arise when there are uncommon manifestations of common arrhythmias, through strict adherence to the “rules” of electrophysiology when exceptions are present, with atypical anatomy, and when 2 or more conditions are present.
Preparing for the ABIM Examination
Authors: Ficalora Robert D.
Published: February 2014

Since 2006, more than 7,000 individuals per year have taken the ABIM initial certification examination, and between 3,000 and 5,000 individuals per year have taken the Maintenance of Certification (MOC) examination. This chapter has the following goals: review the content and format of the American Board of Internal Medicine (ABIM) examination, provide strategies for preparation for the examination, and give suggestions on how to utilize techniques to improve test-taking skills.
Gastroenterology and Hepatology Questions and Answers
Authors: Ficalora Robert D.
Published: February 2014

Chapter 3 presents multiple-choice, board review questions on gastroenterology and hepatology including colon, pancreas, esophagus, stomach, small bowel and intestine, and liver. Full explanations are provided with the correct answers.
Pulmonary Diseases Questions and Answers
Authors: Ficalora Robert D.
Published: February 2014

Chapter 4 presents multiple-choice, board review questions on pulmonary medicine including critical care medicine, diffuse lung disease, occupational lung disease, pulmonary vascular disease, pulmonary embolism, pulmonary hypertension, signs and symptoms, and chest radiographs. Full explanations are provided with the correct answers.