bluuebunny/crossref_metadata_2025 huggingface dataset:
Hypermobility syndromes
Authors: Hakim Alan J. , Grahame Rodney
Published: February 2014

Hypermobility-related syndromes constitute a family of heritable disorders of connective tissue (HDCT) that derive from abnormalities affecting genes that encode for the connective tissue matrix proteins such as collagen, fibrillin, and tenascin. They range from such commonplace though poorly recognized conditions such as the joint hypermobility syndrome (JHS) to the better-known, if more rare, eponymous syndromes such as Marfan's syndrome (MFS) and the different types of the Ehlers-Danlos syndrome (EDS). The more common presentations are with skin pathology (bruising, scaring), joint or spinal and/or muscle pain and instability with vulnerability to injury and chronic widespread pain, cardiac valve pathologies, and in MFS and vascular EDS, arterial dilatation with the risk of dissection and rupture. JHS (widely considered synonymous with the EDS hypermobility type) is further complicated by cardiovascular autonomic dysfunction such as orthostatic intolerance, palpitations, and syncope, and the recently described and commonly encountered pangastrointestinal dysmotility. The latter can manifest as gastro-oesophageal reflux, gastroparesis, slow-transit constipation, or rectal evacuatory dysfunction with rectal intussusception. In addition, HDCT are associated with bladder and uterine problems as a consequence of pelvic floor weakness.
Such multisystemic conditions need to be managed by a multidisciplinary team able to draw on medical, surgical, physical, and psychological interventions by appropriately experienced specialists and therapists.
This chapter introduces the reader to the epidemiology, genetics, classification, and clinical presentation of JHS, EDS, and MFS. It also describes the key investigations required to support a diagnosis and assess complications of an HDCT, as well as the multidisciplinary approach to management.
Haemoglobinopathies
Authors: Rees David
Published: February 2014

Inherited abnormalities of the globin genes are the commonest single-gene disorders in the world and fall into two main groups: thalassaemias and sickle cell disease. Thalassaemias are due to quantitative defects in globin chain synthesis which cause variable anaemia and ineffective erythropoiesis. Thalassaemia was initially thought to be a disease of the bones due to uncontrolled bone marrow expansion causing bony distortion, although this is now unusual with appropriate blood transfusions. Osteopenia, often severe, is a feature of most patients with thalassaemia major and intermedia, caused by bone marrow expansion, iron overload, endocrinopathy, and iron chelation. Treatment with bisphosphonates is generally recommended. Other rheumatological manifestations include arthropathy associated with the use of the iron chelator deferiprone. Sickle cell disease involves a group of conditions caused by polymerization of the abnormal -globin chain, resulting in abnormal erythrocytes which cause vaso-occlusion, vasculopathy, and ischaemic tissue damage. The characteristic symptom is acute bone pain caused by vaso-occlusion; typical episodes require treatment with opiate analgesia and resolve spontaneously by 5 days with no lasting bone damage. The frequency of acute episodes varies widely between patients. The incidence of osteomyelitis is increased, particularly with salmonella, although it is much rarer than acute vaso-occlusion. Avascular necrosis can affect the hips, and less commonly the shoulders and knees. Coincidental rheumatological disease sometimes complicates the condition, particularly systemic lupus erythematosus (SLE) which is more prevalent in populations at increased risk of sickle cell disease.
The sociology of ageing
Authors: Edmondson Ricca
Published: February 2014

This chapter begins with an overview of the contrasting phenomena that need to be reconciled within the sociology of ageing. It stresses respects in which ageing itself is a social phenomenon, arguing that they reveal deep social ambiguities and contestations in connection with the human life-course. It then examines both threats and resources associated with globalised aspects of contemporary ageing, before interrogating contributions by successive theoretical analyses of what ageing involves. The chapter explores the decisive impacts of welfare states on the circumstances of ageing, and their connections with the social distribution of family and caring roles. It continues to a discussion of generational and gender relations before examining wider environments for life-course development and their connections with familial and other forms of mutual care. Lastly, it addresses issues relating to social exclusion and ageism, before exploring aspects of social meaning connected with later life, and their potential for enhancement.
Neurochemical pathology of dementia
Authors: Piggott Margaret Ann
Published: February 2014

This chapter considers the neurodegenerative disorders Alzheimer’s disease (AD), Lewy body dementias (dementia with Lewy bodies (DLB) and Parkinson’s disease dementia(PDD)), frontotemporal dementia (FTD); and also vascular dementia (VaD) which results from cerebrovascular disease. These different conditions, which give rise to dementia syndromes, each have distinct neurochemical pathologies, with important implications for treatment. As increased age is the common risk factor generally associated with dementing illnesses, neurochemical changes are set in the context of the changes which occur during ageing. A detailed understanding of the neurotransmitter function in each condition can lead to rational drug design and treatment strategies appropriate for each group of patients. Neurochemical pathology in transmitter systems underlying clinical features of these disorders are reviewed.
Nonpharmacological interventions in care homes
Authors: James Ian A. , Fossey Jane
Published: February 2014

A large proportion of older people with dementia live in care homes and there has been growing concern in the UK and internationally about the quality of care and inappropriate use of medication for residents. This chapter outlines some of the context and concerns. It goes on to reviews the range of psychosocial interventions available to improve quality of life and well-being of residents and those to treat mental health problems and behaviour seen as challenging. It provides a framework to consider the complex interaction between physical, mental and cognitive health which is required when selecting appropriate treatments. The most common interventions are reviewed and the evidence to support their use outlined, providing an indication of the circumstances in which they may be most helpful.
Care homes for older people
Authors: Dening Tom , Milne Alisoun
Published: February 2014

Although only 5% of the total over 65 population in developed countries lives in a care home, the lifetime risk of needing residential care is considerable. In the UK, 418 000 older people occupy nearly 12 000 care homes; the sector has a total value of around £14 billion. Care home residents tend to be very old, most are women, and most have complex co-morbid needs. Most people enter a care home because they can no longer live independently due to ill health, notably dementia. Dementia affects over two thirds of all residents; physical disability and functional impairment are also common. Behavioural disturbance is common as is depression. There are concerns about excessive reliance on medication, and more emphasis recently has been placed on improving standards of care. Evidence suggests that training and good leadership is effective. With the ageing population, the provision and the funding of care home places will come under increasing pressure. The solutions to this are yet to be determined.
Hello, I’m me! Living well with dementia
Authors: Hennell Brian
Published: February 2014

This chapter is a personal account by a husband and wife, describing the early symptoms of his dementia. From about the age of 67, there were changes in his memory, mood and behaviour and these are described using specific examples. Eventually, after about four years, he was seen by an old age psychiatrist and the diagnosis of frontotemporal dementia was made. This was a great relief to both of them, as the condition had now been recognised and there was help and treatment available. The chapter then details how they have taken positive action to make the best of things and to make what they have learned available to others.
Epidemiology of dementia
Authors: Fratiglioni Laura , Qiu Chengxuan
Published: February 2014

This chapter deals with the occurrence, determinants and primary prevention of dementia. Dementia is one of the major causes of functional dependence, poor quality of life, institutionalisation and mortality among elderly people. The risk of dementia increases almost exponentially with advancing age. As the population ages, dementia poses a serious threat to public health and social welfare system of our society. Accumulating evidence suggests that cardiovascular risk factors significantly contribute to the development and expression of dementia. Thus, adequate management of vascular risk factors and related disorders can be one of the preventative strategies against cognitive ageing and dementia. In addition, psychosocial factors such as educational achievement, socially-integrated and mentally-stimulating lifestyles are critical for delaying the onset of dementia by increasing cognitive reserve. Taken together, maintaining vascular health and adopting a healthy cognitive lifestyle from a life-course perspective may be the most promising strategy to achieve late-life cognitive health.
Vascular and mixed dementias
Authors: Stewart Robert
Published: February 2014

Vascular disease is the most important environmental risk factor for dementia but this research area has been hampered by inadequate outcome definitions – in particular, a diagnostic system that attempts to separate overlapping and probably interacting pathologies. There is now substantial evidence that the well-recognised risk factors for cardiovascular disease and stroke are also risk factors for dementia, including Alzheimer’s disease. However, these risk factors frequently act over several decades, meaning that the chances of definitive randomised controlled trial evidence for risk-modifying interventions are slim. This should not obscure the wide opportunity for delaying or preventing dementia through risk factor control and uncontroversial healthy lifestyles. Care should also be taken that comorbid cerebrovascular disease is not considered as excluding a diagnosis of Alzheimer’s disease, particularly now that this determines treatment eligibility.
Dementia with Lewy bodies and Parkinson’s disease dementia
Authors: Rongve Arvid , Aarsland Dag
Published: February 2014

Dementia with Lewy bodies and Parkinson’s disease dementia belong to the α-synucleinopathies, a family of diseases pathologically characterized by aggregation of α-synuclein in Lewy bodies in the brain. In this chapter we present the epidemiological data for both conditions including new data on MCI. Clinical diagnostic criteria are reviewed and the different neuropathology staging systems for DLB and PDD and the most important genetic findings are considered. Biomarkers in DLB and PDD with particular focus on imaging techniques like CIT-SPECT and MRI are described. Important clinical symptoms in both conditions are presented in detail and the most important clinical differential diagnoses are discussed. Pharmacological and non- pharmacological treatment of different symptoms in both conditions are discussed with particular emphasis on the choline esterase inhibitors and antipsychotic medications.New data on memantine are presented.
Depression in older people
Authors: Thomas Alan
Published: February 2014

Depression remains common in older people. It is strongly associated with physical illnesses and with cognitive impairment and has a complex set of relationships with dementia. Its aetiology involves a complex interplay of physical and psychosocial risk and protective factors. Its neurobiology includes a strong relationship with vascular diseases, neuroendocrine abnormalities, an increase in MRI white matter hyperintense lesions, a reduction in volume of the hippocampus and frontal and subcortical structures and neuronal abnormalities in such structures. Management involves physical (mainly drugs but also ECT) and psychological treatments. In the acute phase remission is the aim, and following this continuation and maintenance stages should continue with the same treatments indefinitely. Prognosis overall is not as good as in younger adults, but this is largely due to the presence of cognitive deficits and physical ill health.
Manic syndromes in old age
Authors: Vasudev Akshya
Published: February 2014

Manic syndromes in the elderly are different from those seen in the younger bipolar population. They are a heterogenous group but can probably be divided into two main groups based on age of onset of the illness: late onset bipolar disorder (LOB) and early onset bipolar disorder (EOB). This chapter elaborates on differences in these two groups based on epidemiological data findings, clinical presentation, aetiopathogenesis and management. Latest concepts with regards to the vascular mania hypothesis, neuroimaging findings, cognitive impairment in bipolar disorder are also dealt with. A critical review of pharmacological management options is also provided with reference to recently published data on mood stabilisers, antipsychotic and antidepressant usage for this age group.
Alcohol and substance abuse in older people
Authors: O’Connell Henry , Lawlor Brian
Published: February 2014

This chapter highlights the importance of alcohol use disorders (AUDs), inappropriate medication use (IMU) and use of illicit drugs in older people. Such problems are associated with considerable morbidity and will become more important with the ageing ‘baby-boomer’ generation in coming years. AUDs are under-detected, misdiagnosed and often completely missed in older populations. However, despite ageist and pessimistic assumptions, AUDs in older people are as amenable to treatment as in younger people. IMU in older people includes abuse of prescribed medications such as benzodiazepines and opiates, unnecessary treatment of medical and psychiatric conditions and toxic drug reactions related to inappropriate polypharmacy. Screening and treatment programmes for IMU could lead to considerable improvements in individual and population health. Misuse of illicit drugs, e.g. marijuana, cocaine, opioids and stimulants, by older people is not yet a major problem, but will probably become more prevalent and be a more important clinical issue for future generations of older people.
Personality in later life: personality disorder and the effects of illness on personality
Authors: Oppenheimer Catherine
Published: February 2014

This chapter covers disorders of personality in later life, including personality changes caused by dementia. There is little agreement on how best to measure personality in old age. Nevertheless, it is clear that specific changes in personality accompany dementia, particularly fronto-temporal dementia. Personality disorder (PD) in older people has been little studied and is beset by problems of definition. The current (DSM-IV) categories of PD need modification to take account of the biological and cultural contexts of old age before valid studies of the epidemiology and the life course of PDs can be made. An older person’s personality style will profoundly influence their adjustment to major life-stresses, and good care depends on clinicians’ understanding of this. Long-standing personality traits are probably important in the development of the Diogenes syndrome (extreme self-neglect) in later life.
Sexuality in later life
Authors: Bouman Walter Pierre
Published: February 2014

Sexuality in later life gives a comprehensive overview concerning all aspects of sexuality and ageing. It starts with discussing myths and attitudes to later-life sexuality, followed by a review of research studies in this area, sexual physiology and the effects of physical illness and medication on sexuality, taking a sexual history, the description of the main sexual problems in older people and addressing specific issues of the lesbian, gay, bisexual and transgender (LGBT) population. It further describes the issue of sexual abuse in older people and the topic of sexuality and dementia. The chapter concludes with a discussion of the management of a variety of sexual problems encountered in clinical practice.
Ethics of living and dying with dementia
Authors: Hertogh Cees , van der Steen Jenny
Published: February 2014

The gradual progression of dementia means there has to be a constant search for a reasonable balance between supporting autonomy and ensuring proper representation. ∙ Good end of life care for people with dementia depends on adequate advance care planning, startling early in the disease process ∙ Where possible, it involves striving for joint decision-making with the patient and next-of-kin about (future) medical treatment and (future) care. ∙ Written advance directives may support representatives of incompetent patients in their role of surrogate decision maker, but the contents of the directive require interpretation in the context of advance care planning. ∙ The concept of “palliative care” offers a (policy) framework for advance care planning as well as moral guideline for dealing with written advance directives of patients with dementia.
Special problems for psychiatric classification
Authors: Cooper John E. , Sartorius Norman
Published: February 2014

In this chapter there are comments upon a number of problems that are of particular importance in psychiatric classifications. There has been some agreement that social problems should be kept conceptually separate from mental and physical disease, but a satisfactory short definition of mental disease has proved elusive. In the background of this debate is the question of what is the basic responsibility of a modern scientifically trained doctor. Is it to just detect and treat physical illness, or does it include the relief of the whole illness experience of the patient and family? Kraupl Taylor and Fulford have argued strongly ‘for the latter. Compilers of modern classifications of mental disorders have avoided the debate about definitions of disease by using the conveniently imprecise concept of ‘disorder’. The definitions of this in ICD-10 and DSM-IV are similar, but there is an important difference that is easily overlooked, concerning the inclusion of interference with social functions.
Psychiatric classification in a wider perspective
Authors: Cooper John E. , Sartorius Norman
Published: February 2014

The generation of numerous proposals for classifications of psychiatric disorders began in the late decades of the 19th Century and continued without interruptions until the second half of the 20th Century. These classifications were based on different principles such as presumed etiology, clinical syndromes, and course and outcome of illness; Stengel’s review for the WHO showed that their diversity made it impossible to compare results of research or develop universally valid recommendations concerning the management of mental disorders. The programme which the World Health Organization started in the 1960s had the aim of developing a classification that would be generally accepted internationally, and would serve as a common language in the field of mental health. Together with the Diagnostic and Statistical Manual produced by the American Psychiatric Association, it has had an international influence, leading to a significant reduction of the numbers of proposals for national and regional classifications. The current versions of the ICD-10 Chapter V and the DSM-IV of the APA’s lassification are largely similar, and continuing cooperation between those preparing the next versions should ensure that this similarity is not lost. Whether any additional sections are needed to describe ‘culture-specific’ disorders which only occur in particular cultures is not yet known. Special sections are present in both the WHO classification and in DSM-IV to encourage research into this possibility.
Constrictive pericarditis
Authors: Katritsis Demosthenes G. , Gersh Bernard J. , Camm A. John
Published: February 2014

Constrictive pericarditis and its differential diagnosis from restrictive cardiomyopathy are presented. Therapy of the condition is discussed.
Pseudoaneurysms of the heart
Authors: Katritsis Demosthenes G. , Gersh Bernard J. , Camm A. John
Published: February 2014

Diagnosis, therapy, and prophylaxis of rheumatic fever are discussed.
Development of the trauma intensive care unit within trauma systems
Authors: Mohan Deepika
Published: February 2014

The modern trauma intensive care unit (ICU) reflects the confluence of twotrends: the development of inclusive trauma systems and the rise of subspecialtyintensive care units. This chapter will review key historical events that influencedthe development of the trauma ICU within trauma systems, as well assome of the literature on the current role of the trauma ICU in the managementof trauma patients.
Massive transfusions and coagulopathy
Authors: Neal Matthew D. , McDaniel Lauren M. , Forsythe Raquel M.
Published: February 2014

Numerous definitions of massivetransfusion (MT) exist, but it is most commonly defined as the administrationof ≥ 10 units of packed red blood cells (pRBCs) to a patient in a single 24-hourperiod. The need for MT in the ICU arises most commonly in the setting oftraumatic injury because 3%–5% of all civilian trauma patients go on to require MT. Postoperative hemorrhage, postpartum complications, complex electivevascular and transplantation surgery, and acute gastrointestinal bleeding arealso frequent triggers for massive transfusion. This chapter will discussthe approach to MT for the patient presenting with hemorrhagic shock, with afocus on the evidence-based approach to hemostatic resuscitation as well as theimportant consequences and complications that must be closely monitored bythe ICU clinician.
Ventilator management of trauma patients
Authors: Benns Matthew , Sarani Babak , Corcos Alain C.
Published: February 2014

The indications for mechanical ventilation in the trauma patient falls into three, broad categories: shock resulting in metabolic acidosis, insult to the respiratorysystem resulting in impaired gas exchange, and depressed mental status leadingto decreased ability to protect the airway. Once mechanical ventilation has beeninitiated, the clinician must be cognizant of the possibility of ventilator-inducedlung injury. It is critical to recall that oxygen exchange isdirectly proportional to the fraction of inspired oxygen (FiO2) and mean airwaypressure, while CO 2 exchange is directly proportional to the minute ventilation.
Endocrinology in the critically injured patient
Authors: Patel Nimitt , Sperry Jason
Published: February 2014

Although significant advances in the care of the injured patient have occurredover the last decade, those who survive their initial injury continue to be plaguedwith the development of multiple organ failure, sepsis, and their attributablemorbid effects. In these critically injured patients there are many stressors inaddition to their injuries, such as infectious complications, various therapeuticinterventions, and operative procedures. An injured patient–s ability to cope with these factors comprisesa complex multi-factorial response in which the endocrine system–s involvement, integrity, and flexibility are integral components for survival. The neuroendocrineresponse is a key factor in maintaining homeostasis and enablingthe injured patient to recover.
Hypothermia and trauma
Authors: Tisherman Samuel A.
Published: February 2014

Spontaneous, uncontrolled hypothermia occurs in up to half of the victims ofmajor trauma. Trauma patients are unable to maintain normal temperaturehomeostasis because of the effects of shock, alcohol and drug intoxication, sedation, and anesthesia. Anesthesia alone may decrease heat production by 20%. Inaddition, the administration of room-temperature fluids and exposure for evaluationand operative interventions can increase heat loss. The more severe theinjury, the greater the risk of hypothermia.
Toxicology
Authors: Katz Kenneth D.
Published: February 2014

Poisonings, intoxications, and withdrawal states are frequently encounteredin the trauma patient. Consequently, the clinician must be familiar with the generalapproach to diagnosis and treatment of common toxicological entities.Furthermore, the initial traumatic injury, treatment, or diagnostic studies may maskor delay recognition of an underlying overdose, which can easily impact outcome.The initial approach to the poisoned patient focuses primarily on history, physicalexamination, and targeted diagnostics.Particular attention should bepaid to the patient presenting with clinical findings incongruous with the history, physical examination, or diagnostic studies.Routine diagnostic studies for the toxicology patient are often intertwined with those for the trauma patient, but, more specific laboratory testing should be guided by clinical presentation and suspicion.
Legal issues in trauma intensive care
Authors: Kidwell Richard P.
Published: February 2014

Critically ill trauma patients are at high risk for complications and death. The factthat there may be legal proceedings related to the original injury further adds tothe fear of litigation for physicians caring for trauma patients. Most of this fear isungrounded, however. There is a paucity of reported appellate court opinionsregarding trauma cases. Thus, there is little guidance from courts to delineatewith any degree of clarity the expected standard of care with respect to traumapatients in the Intensive Care Unit (ICU).
Meninges and Ventricular System
Authors: Fisch Adam
Published: February 2014

Chapter 2 discusses how to draw the meninges and ventricular system, including cerebrospinal fluid (CSF) flow, the cerebral ventricles, the cisterns, sinuses, and veins, as well as hemorrhages and innervation.
Cranial Nerves 5, 7, 9, 10
Authors: Fisch Adam
Published: February 2014

Chapter 13 discusses cranial nerves 5, 7, 9, 10, and their peripheral innervation, nuclei, tracts, anatomy, as well as the gag reflex.
Cognition
Authors: Fisch Adam
Published: February 2014

Chapter 24 discusses cognition, including language disorders, classes, capacity, and consolidation of memory, and apraxia and neglect.
Agitated Delirium
Authors: Levin Morris
Published: February 2014

Chapter 2 presents a case regarding agitated delirium, and discusses risks to both patient and medical team, sedation to be given when necessary, initial treatment for delirium, head CT where needed, LP in cases of meningitis and encephalitis, and suspected drug intoxication, including over-the-counter, prescription, and illicit drugs.
Principles of Electrophysiology
Authors: Lambe Evelyn K.
Published: February 2014

Electrophysiology is an essential tool to measure basic neuronal properties and assess how neurons communicate with each other. Electrophysiological approachesgive access to a higher level of resolution than most brain-imaging methods, and demonstrate which receptors and channels are in the membrane and able to affect neuronal function. Such cellular and temporal resolution is valuable to show how neuronal communication is altered in rodent models of human mental illness and by psychoactive drugs and medicines. The chapter begins with a review of neuronal physiology, discusses the typical tools used by electrophysiologists, and then gives examples of how electrophysiological approaches are relevant to understanding the neurobiology and treatment of mental illness.
Epigenetics of Psychiatric Diseases
Authors: McGill Bryan E. , Zoghbi Huda Y.
Published: February 2014

Epigenetics refers to changes in gene expression that occur without altering the underlying deoxyribonucleic acid (DNA) sequence. Epigenetic changes can be faithfully inherited and replicated through generations of somatic cell division. Furthermore, epigenetic changes result in stable phenotypic alterations for the organism. In recent years, a number of molecular pathways have been identified that mediate the establishment, maintenance, and interpretation of the epigenetic code. In this chapter, we provide a brief primer on the epigenetic mechanisms that are currently known to exist in humans: DNA methylation, covalent histone modification, chromatin remodeling by PolycombGroup (PcG) and trithorax-Group (trxG) proteins, ribonucleic acid (RNA) interference, and imprinting. Following that, we discuss examples whereby errors in these processes contribute to the pathogenesis of psychiatric diseases.
Genomic Syndromes in Schizophrenia
Authors: Kirov George , O’Donovan Michael C. , Owen Michael J.
Published: February 2014

Several submicroscopic genomic deletions and duplications known as copy number variants (CNVs) have been reported to increase susceptibility to schizophrenia. Those for which the evidence is particularly strong include deletions at chromosomal segments 1q21.1, 3q29, 15q11.2, 15q13.3, 17q12 and 22q11.2, duplications at 15q11.2-q13.1, 16p13.1, and 16p11.2, and deletions atthe gene NRXN1. The effect of each on individual risk is relatively large, but it does not appear that any of them is alone sufficient to cause disorder in carriers. These CNVs often arise as new mutations(de novo). Analyses of genes enriched among schizophrenia implicated CNVs highlight the involvement in the disorder of post-synaptic processes relevant to glutamatergicsignalling, cognition and learning. CNVs that contribute to schizophrenia risk also contribute to other neurodevelopmental disorders, including intellectual disability, developmental delay and autism. As a result of selection, all known pathogenic CNVs are rare, and none makes a sizeable contribution to overall population risk of schizophrenia, although the study of these mutations is nevertheless providing important insights into the origins of the disorder.
Cognitive and Motivational Neuroscience of Psychotic Disorders
Authors: Anticevic Alan , Dowd Erin C. , Barch Deanna M.
Published: February 2014

Schizophrenia is a complex neuropsychiatric syndrome presenting with a constellation of symptoms. Clinicians have long recognized that abnormalities in cognitive function and motivated behavior are a key component of psychosis, and of schizophrenia in particular. Here we postulate that these deficits may reflect, at least in part, impairments in the ability to actively maintain and utilize internal representations of emotional experiences, previous rewards, and motivational goals in order to drive current and future behavior in a way that would normally allow individuals to obtain desired outcomes. We discuss the evidence for such impairment in schizophrenia, how it manifests in domains typically referred to as executive control, WM and episodic memory, and how it may help us understand impairments in reward processing and motivation in schizophrenia.
Molecular and Cellular Pathogenesis of Depression and Mechanisms for Treatment Response
Authors: Duman Ronald S.
Published: February 2014

Early theories of depression were centered on the monoamines, but more recent work has focused on the amino acid neurotransmitters, glutamate and GABA. Imbalances of glutamate and GABA transmission in key cortical and limbic structures are thought to contribute to disruption of brain circuits that control emotion and mood. These imbalances, together with stress activated pathways that regulate neurotrophic factors and inflammatory cytokines could contribute to atrophy and loss of neurons observed in depressed patients and rodent stress models. The significance of synaptic connections in depression is highlighted by new studies demonstrating that a rapid acting, highly efficacious antidepressant agent increases synaptogenesis, paving the way for a new generation of medications for the treatment of depression.
Pathogenesis of Depression: Clinical Studies
Authors: Furey Maura A. , Mathews Daniel C. , Zarate Carlos A.
Published: February 2014

Historically, research focused on themonoaminergicsystemshas contributed to our understanding of theunderlying pathophysiology of affective disorders.Recent directions in clinical and translational research have concentrated on discovering alternative therapeutic targets with the hopes of producing more efficacious and faster-acting antidepressant agents.This chapter offers an overview of recent clinical research targeting the glutamatergic and cholinergic neurotransmitter systems, with particular interest in novel agents that have produced rapid antidepressant effects. Insights into the underlying pathophysiology of mood disorders resulting from this work are reviewed. In addition, the rapidity of clinical response offers the unique opportunity to studybiological markers more efficiently , and to utilize biomarkers to predict treatment outcome. The findings from such studies also are summarized.
Neural Circuitry of Depression
Authors: Price Joseph L. , Drevets Wayne C.
Published: February 2014

The primary mood disorders, major depressive disorder (MDD) and bipolar disorder (BD), constitute leading causes of disability on a global scale, yet little is known about their pathogenesis. These conditions are not associated with gross brain pathology or clear animal models for spontaneous recurrent mood episodes.Thus, the development of neuroimagingtechnologies that allowin vivo characterization of anatomy, physiology, and neurochemistryin human subjects withmood disorders has enabled significant advances toward elucidating their pathophysiology. Crucially, the interpretion of abnormalities found using these technologies in mood disorders has depended upon the concomitant delineation of anatomical networks that support emotional behavior.

Early studies identified the amygdala, hippocampus, and other parts of what was termed the “limbic” system as central parts of the emotional brain. Beginning in the 1970’s and 1980’s and continuing through the last 15 years, neuroanatomical techniques based on axonal transport have been applied extensively to the limbic system and prefrontal cortex of monkeys. With these methods, a system has been described that links the medial prefrontal cortex and a few related cortical areas to the amygdala, the ventral striatum and pallidum, the medial thalamus, the hypothalamus, and the periaqueductal gray and other parts of the brainstem. A large body of human data from functional and structural imaging, as well as analysis of lesions and histological material indicates that this system is centrally involved in mood disorders.
Neurobiology of Fear and Anxiety: Contributions of Animal Models to Current Understanding
Authors: Cain Christopher K. , Sullivan Gregory M. , LeDoux Joseph E.
Published: February 2014

Counting significant procedural variations, there are at least 100 different animal models of fear and anxiety. Here we summarize the contribution of animal models to our current understanding of neurobiological mechanisms and discuss important distinctions such as: 1) feelings vs. defensive responding, 2) the relevance of models to fear vs. anxiety processes, 3) pharmacology- vs. neurocircuit-based models, 4) unconditioned vs. conditioned models, 5) models of state vs. trait anxiety, 6) models of fear/anxiety excitation vs. inhibition, and 6) models of normal vs. abnormal responding. We argue that models amenable to neurocircuit analysis, especially those based on threat conditioning of defensive responses, are likely to provide a deeper understanding of anxiety mechanisms and facilitate the discovery of novel treatments.
Differential roles of GABA Receptors in Anxiety
Authors: Möhler Hanns
Published: February 2014

By controlling spike timing and sculpting neuronal rhythms, GABAergic interneurons play a key role in regulating neuronal circuits and behavior. The extensive diversity of interneurons is paralleled by a pronounced heterogeneity of corresponding GABAA receptors. Through their distinct regional and domain-specific location, the GABAA receptor subtypes are markers for diverse neuronal circuits and give rise to a correspondingly diverse pharmacology. α‎1 GABAA receptor subtypes mediate sedation and are the target for sedative-hypnotics such as zolpidem. α‎2 and α‎3 receptor subtypes mediate anxiolytic activity (including value arbitration) devoid of sedation. α‎5 receptor subtypes control memory performance and give rise to memory enhancing drugs. Microcircuits, identified in cerebral cortex, hippocampus and amygdala provide insights into the functional readout of GABAA receptor subtypes, particularly in the regulation of anxiety and fear and of memory performance.
Brain Development and the Risk for Substance Abuse
Authors: Caudle Kristina , Casey B.J.
Published: February 2014

Drug and alcohol dependence affects millions each year. Adolescence is a period of increased risk for substance use disorders. Understanding how the brain is changing during this developmental window relative to childhood and adulthood and how these changes vary across individuals is critical for predicting risk of later substance abuse and dependence. This chapter provides an overview of recent human imaging and animal studies of brain development focusing on changes in corticostriatal circuitry that has been implicated in addiction. Behavioral, clinical, and neurobiological evidence is provided to help elucidate who may be most at risk for developing a substance abuse problem and whenthey may be most vulnerable.
Brain, Reward, and Drug Addiction
Authors: Pariyadath Vani , Paulus Martin P. , Stein Elliot A.
Published: February 2014

Drug addiction is an important health and societal issue. Dysregulation of reward, such as increased sensitization of incentive salience or greater sensitivity to the withdrawal from reward-related drug effects, has been implicated in this complex and multifaceted disease. Research from the past several years has de-emphasized the role of dopaminergic function within the basal ganglia in favor of an expanding reward network with extensive connectivity between multiple reward circuit nodes and utilizing multiple transmitter systems. Such a paradigm shift has required a reformulation in understanding the neural mechanisms underlying positive and negative reinforcement. Neuroimaging provides unique opportunities for probing multi-node interactions, and thus can assist in better understanding reward and "anti-reward" mechanisms underlying the normal and addiction phenotype. The goal for future neuroimaging research is to better inform the clinical aspect of drug addiction by determining the propensity to develop drug addiction, assessing severity of addiction, predicting treatment outcome, and facilitating individualized treatment regimens.
Pharmacotherapy of Substance Use Disorders
Authors: Acri Jane B. , Skolnick Phil
Published: February 2014

Despite remarkable progress in our understanding of the neurobiological bases of drug abuse, no novel pharmacotherapies have recently been approved to treat substance use disorders (SUDs). Thus, while reformulations of established treatments have either been approved or are currently in late stage development (e.g., sustained release formulations of naltrexone [Vivitrol®] and buprenorphine [Probuphine®]), the development of medications to treat SUDs has lagged well behind other areas of psychiatry. In this chapter, we review some of the factors that have contributed to this dearth of innovative pharmacotherapies. We also review evidence that supports clinical testing of late stage molecules (developed for other indications) acting at two promising targets, as well as novel biological approaches to the treatment of SUDs.
Experimental Animal Models of Alzheimer’s Disease
Authors: Morgan Dave
Published: February 2014

Animal models of human disease provide opportunities to learn more regarding the mechanisms responsible for the disease process and provide a platform in which to screen therapeutic agents. Earliest rodent models provided platforms in which to test symptomatic treatments. More recent platforms injecting Aβ‎ are providing information regarding mechanisms of toxicity. Finally, the success in finding transgenic amyloid precursor protein constructs that lead to a measureable cognitive phenotype and amyloid deposits resembling those in Alzheimer’s disease permit screening of anti-amyloid agents intended for clinical testing. Although imperfect, these experimental models have permitted scientists to learn a bit more about the mechanisms of dementia.
Current Therapies for Alzheimer’s Disease
Authors: Sano Mary , Neugroschl Judith
Published: February 2014

Dementia and Alzheimer’s disease effects more than 5million people in the US yet the treatment options are minimal. There are five medications representing 2 classes of drugs that were approved by the US FDA between 1994 and 2003 and they provide modest effect on clinical outcomes. In the past decade medical foods have also become available with a specific indication for Alzheimer’s disease. Though once promising, rigorously conducted clinical trials, have demonstrated the lack of efficacy of several agents including anti-inflammatory and anti-oxidant agents, hormones, agents that modify cardiovascular and metabolic risk and a number of vitamins and nutritional supplements. Enthusiasm remains high for identifying agents to modify brain specific insulin resistance and to improve synaptic function and reduce cell death.
Lewy Body Dementias
Authors: Karantzoulis Stella , Galvin James E.
Published: February 2014

Lewy body dementia (LBD) includes both Parkinson’s disease dementia (PDD) and dementia with Lewy bodies (DLB) and affects between 1 and 2 million older Americans. LBD is a multi-system disorder, involving disturbances of movement, cognition, behavior, sleep and autonomic function. LBD consensus diagnostic criteria exist but are somewhat lacking in sensitivity. Diagnosis of LBD is complicated by overlapping symptoms with the pure dementia phenotype of Alzheimer’s disease (AD), the pure motor phenotype of PD, and psychotic and behavioral features common in psychiatric disease. Early diagnosis is critical as LBD patients may respond differently than AD patients to certain dementia and behavioral treatments. Traditional neuroleptics should be avoided, due to potentially severe side effects. Optimum management of LBD includes both pharmacological and non-pharmacological treatments for the patient, and education and support for caregivers. This chapter reviews current knowledge of LBD aimed at facilitating early diagnosis and knowledge of LBD treatment options.
The Infirmities of Psychiatric Diagnosis
Authors: Hyman Steven E.
Published: February 2014

The major classifications of mental disorders are undergoing revision. Given the high stakes, the revision processes are both serious and contentious. Yet the relatively conservative results of these revisions do not address the fundamental structural flaws of their predecessor volumes, notably the conceptualization of mental disorders as narrowly defined, discontinuous categories. The narrow, categorical definitions produce artifactual comorbidity in many patients while failing to capture the symptoms of many others. leading to diagnoses “not otherwise specified”. Yet the patients included within most diagnostic categories remain heterogeneous. The diagnoses within the standard manuals should be treated as rough guidelines that should not be permitted to impede scientific discovery. Alternative approaches are in desperate need that recognize the dimensional nature of psychopathology and better capture its core etiological characteristics, heterogeneity and polygenicity.
Reentry, Transient Entrainment, and Concealed Entrainment
Authors: Shen Win-Kuang
Published: February 2014

The primary objective of this chapter is to provide essential information as a reference to dissect the arrhythmogenic mechanisms useful in clinical practice. Reentry, transient entrainment, and concealed entrainment are reviewed.
Case 13
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 palpitations, ventricular tachycardia, syncope, radiofrequency ablation, noncontact mapping, and the right and left ventricular outflow tracts.
Infectious Diseases Questions and Answers
Authors: Ficalora Robert D.
Published: February 2014

Chapter 5 presents multiple-choice, board review questions on infectious diseases including travel medicine, zoonoses, bioterrorism, pneumonia, mycobacterial infections, skin and soft tissue infections, bone and joint infections, urinary tract infections, sexually transmitted infections, gastrointestinal tract infections, and HIV infection. Full explanations are provided with the correct answers.
Differential Diagnosis
Authors: Abou-Khalil Bassel , Misulis Karl E
Published: February 2014

The dictionary definition of seizure includes events caused by epileptic discharges as well as non-epileptic events. In medicine we distinguish between epileptic and non-epileptic events, based on whether there is a cerebral electrical discharge responsible for the event. Other conditions which can clinically resemble epileptic seizures include syncope, psychogenic non-epileptic seizures, some movement disorders, and others. The differential diagnosis of seizures and clues to diagnosis are discussed.
Psychoanalysis, Apparatus Theory, and Subjectivity
Authors: Buhler James
Published: February 2014

This chapterexamines the relevance of psychoanalysis, subjectivity, and apparatus theory to film music studies. It explains that psychoanalysis provides the theory of subjectivity of the formation of social subjects, while critical use of psychoanalysis is unconcerned with clinical treatment and is interested in turning psychoanalysis back on itself in order to examine how it formulates the norm. It considers the relevant works of philosopher and cultural critic SlavojŽižek and Jean-Louis Baudry, who developed the idea ofcinematic apparatus.
Film Music from the Perspective of Cognitive Science
Authors: Cohen Annabel J.
Published: February 2014

This chapterexamines how the effects of film music on meaning, memory, and the construction of a reality within a film can be addressed or understood from a cognitive scientific perspective. It reviews studies that aim to explain why music is important to film as well as how music functions in film, and it discusses the principles of cognitive science and cognitive perspective. It also considers the Congruence-Associationist Model for understanding filmmusic, which was developed to account for the fact that the attitudes toward three geometric film characters were affected differently by background music.
Performance Practices and Music In Early Cinema outside Hollywood
Authors: Kalinak Kathryn
Published: February 2014

This chapterexamines the diversity of international practices in film music outside Hollywood during the silent film era. It describes performance practices around the globe and offers a broader context in which to consider American practices during this period. It suggests that music functioned as a cultural interface throughout the silent era in a way quite different from the sound era and that music in the silent era had an impressive power to interact with moving images in ways not controlled by films or their producers.
Listening In Film
Authors: Kielian-Gilbert Marianne
Published: February 2014

This chapterexamines issues related to the potential of “vivid listening” for music’s temporal figurations in and of material contexts. It considers how listening in film becomes a problem for analysis, and analyzes how recontextualizing music in cinematic settings interacts with experiences of their temporal unfolding. It discusses the different aspects or components of listening in film and in music, and suggests that listening in/to music and listening to/in film differ from processing and figuring a score or scenario.