bluuebunny/crossref_metadata_2025 huggingface dataset:
Basic mechanisms and treatment planning/targets for attention-deficit/hyperactivity disorder
Authors: Franke Barbara , Buitelaar Jan K.
Published: March 2020

The mechanisms underlying ADHD are complex and can be defined at different levels. Cognitive deficits are often part of the disorder, including problems in executive functioning, reward processing, and timing deficits. Alterations have also been reported in brain structure and function in people with the disorder. ADHD is known to be a highly heritable, multifactorial disorder, in which genetic factors—often in combination with environmental factors—are risk factors for disease onset. Early research at the genetic level has implicated monoaminergic neurotransmission, following the serendipitous finding that methylphenidate, a dopamine and noradrenaline transport inhibitor, treats ADHD symptoms. The current models to explain brain malfunctioning in ADHD indeed centre around these monoamine systems. In addition to dopamine, noradrenaline, and (to a lesser extent) serotonin, also glutamate, histamine, and the nicotinic acetylcholinergic system seem to be involved in ADHD aetiology. In the coming years, genetic research is expected to uncover more of the mechanisms underlying ADHD, hopefully resulting in improved treatment options.
Insights from neuroanatomical imaging into attention-deficit/hyperactivity disorder throughout the lifespan
Authors: Shaw Philip , Szekely Eszter
Published: March 2020

The relatively recent advent of magnetic resonance imaging has given us an invaluable ‘window’ into the brain in attention-deficit/hyperactivity disorder (ADHD). This chapter reviews the literature on the structural neuroimaging of ADHD throughout the lifespan. Meta-analyses and large individual studies converge to find anomalies in the basal ganglia in ADHD; some appear developmentally stable, while others are progressive. Compromise of the cerebral cortex and cerebellum are also commonly reported, and developmental trajectories of these structures have been linked with the highly variable clinical course of the disorder. ADHD can be considered dimensionally, lying at the extreme end of a continuous distribution of symptoms and underlying cognitive processes. Some studies find such dimensionality is also present in ADHD-related neuroanatomical change. Pilot studies have examined how variation in some candidate genes is tied to neuroanatomy in the disorder. Studies at the level of the entire genome await much larger cohorts.
Pathways of neurodegeneration underlying dementia
Authors: Buckley Noel J. , Tofaris George K.
Published: March 2020

Neurodegenerative diseases (NDDs) and dementia are the greatest disease burdens of our time, carrying an enormous personal, societal, and economic burden. Although NDDs are often thought of as individual entities in their clinical presentation, there is increasing evidence of considerable overlap of their aetiology and pathogenesis. This has led to the discovery of overlapping biological processes underlying disease mechanisms, including protein misfolding, endoplasmic reticulum stress, cellular transport, mitochondrial dysfunction, and inflammation. These biological processes ultimately result in neuronal death and attendant disease symptomology, but pathogenesis of NDDs is orchestrated by an intimate interaction of both neuronal and non-neuronal cells. We are now moving into an era where we have new human cellular models, novel genetic manipulation tools, and high-throughput single-cell analysis techniques that allow interrogation of this commonality and complexity, married to an aspiration to develop novel therapeutic strategies to delay, slow, or reverse neurodegeneration. This chapter provides a brief summary of these evolving ideas.
Delirium
Authors: Bhat Ravi S. , Rockwood Kenneth
Published: March 2020

Delirium is a common term for an ancient condition that still defies precise categorization or treatments based explicitly on its pathophysiology. Understanding has proved evanescent. For example, even a tried-and-true distinction between delirium and dementia appears not to withstand precise scrutiny. A newer understanding of the pathophysiology of delirium focuses on the role of neuroinflammation in both engendering vulnerability in the ageing and/or cognitively impaired brain and, when unwell with systemic disease, precipitating delirium. In the meantime, useful effort has focused on prevention, especially by multicomponent interventions. Treatment proceeds by addressing any precipitating illnesses and by general measures, including empathetic, personalized care. A role exists for dopamine antagonist medication, but it must be used with a precise indication and with early and frequent review. The prognosis of delirium is now understood to be often less transient than had originally been proposed, especially when it occurs in older people, in many of whom it can unmask, or even precipitate, dementia. Future research should extend to elderly people, who, in any setting, develop delirium, and evaluate mechanisms that lead to the characteristics features of delirium.
Alzheimer’s disease
Authors: Koychev Ivan , Gallacher John
Published: March 2020

Alzheimer’s disease is the primary cause of dementia, accounting for over 70% of all cases. The disease starts decades before the first symptoms and involves misfolding of amyloid and tau proteins, leading to intra- and extracellular protein accumulations. The early clinical presentation is dominated by loss of short memory (amnestic phenotype), but other atypical presentations can occur with dominant visual agnosia, word-finding difficulties, or change in character and disinhibition. Later stages feature loss of procedural skills and disorientation, but also changes to behaviour (psychosis, depression, agitation, apathy), and ultimately the condition leads to complete loss of independence. Efforts to develop disease-modifying therapies have so far been unsuccessful, with the only currently licensed treatments focusing on short-term improvement in attention and memory. However, primary and secondary prevention has the potential to significantly alleviate the burden associated with Alzheimer’s disease, as up to a third of all sporadic cases are due to modifiable risk factors.
Vascular cognitive impairment
Authors: Byars Joanne A. , Jorge Ricardo E.
Published: March 2020

Vascular cognitive impairment (VCI)—vascular dementia (VasD) in its severe form—is cognitive impairment due to cerebral ischaemic or haemorrhagic disease. VasD is the second most common cause of dementia in the United States. VCI and Alzheimer’s disease can coexist and synergistically worsen each other. Clinical features of VCI can vary, depending on which areas of the brain the vascular pathology affects. Individuals without a history of clinical stroke can still have VCI; small-vessel cerebrovascular disease can present as an insidious cognitive decline, rather than an abrupt functional change. Neuroimaging plays a key role in diagnosing VCI and distinguishing it from other aetiologies of cognitive impairment. Aggressive vascular risk factor modification helps prevent VCI and improves outcomes in VCI, and represents the most important intervention for this condition. Early detection of VCI maximizes the effectiveness of vascular risk factor modification. Cholinesterase inhibitors and memantine may offer some cognitive benefit in VCI.
Substance use disorders and the mechanisms of drug addiction
Authors: Robbins Trevor W. , Everitt Barry J.
Published: March 2020

The understanding of drug addiction has gained much from a neuroscientific approach, reflected by changing approaches in diagnosis. The two main psychological accounts of addiction to substances, ranging from alcohol and nicotine to opioids and stimulant drugs, are opponent motivational processing, emphasizing the importance of withdrawal symptoms, and aberrant learning from positive reinforcement. The neural and neurochemical systems implicated have been identified on the basis of animal studies, using especially the self-administration paradigm, and human investigations employing a range of brain imaging modalities. These neural substrates include dopamine-dependent functions of the ventral and dorsal striatum, as well as regulatory influences of fronto-limbic systems. The chapter considers the critical issue of cause and effect, and whether brain changes reflect neurotoxic effects of abuse or whether there are predisposing neurobehavioural factors. It also outlines the current situation and future prospects for treatment by medication, possibly in association with psychological approaches.
Alcohol use disorder
Authors: van den Brink Wim , Kiefer Falk
Published: March 2020

Alcohol is one of the most frequently used substances, and alcohol-related disorders are common, especially in western societies. While there is no safe lower drinking level, a clear dose–response relationship has been shown between alcohol intake and organ damage. Conceptualization and diagnostic classification of alcohol use disorders have changed over time, focusing most recently on aspects of craving, loss of control, and continued use despite negative consequences. Alcohol acts via various binding sites in the brain and via downstream effects, including glutamatergic, GABAergic, serotonergic, dopaminergic, opioid, and neuroendocrine pathways. For its long-lasting, habit-forming effects, sensitization within the mesolimbic–mesocortical system is crucial. Psychological treatments traditionally focus on motivational enhancement, cognitive behaviour therapy, and the community reinforcement approach. Pharmacological treatment approaches range from aversive and reward-inhibiting to anti-craving compounds and cognitive enhancers, which target opioid, glutamatergic, and monoamine receptors. Improvement of treatment effects can be achieved by polypharmacy and use of personalized medicine, based on clinical characteristics, biomarkers, and genetic indicators.
Comorbidity of substance use and psychiatric disorders
Authors: Sinclair Julia M.A. , Lingford-Hughes Anne
Published: March 2020

Comorbidity of psychiatric disorders with alcohol or other substance use is common and has a significant negative impact on patient outcomes. The evidence base for treatments for comorbid conditions is less robust than for single disorders, but it is clear that active management of both conditions is required. Systematic screening of all patients for alcohol and other substance use should be an integral part of assessment, as well as understanding patient goals for any treatment plan. Assessment focused on the interaction and impact of the comorbidity for the individual patient, rather than trying to determine which is primary, is likely to be beneficial for both patient and clinician. Pharmacological and psychological treatments for the management of alcohol and substance use disorder have also been shown to be effective in patients with comorbid psychiatric conditions but are not considered frequently.
Antipsychotic and anticholinergic drugs
Authors: Meltzer Herbert Y. , Bobo William V.
Published: March 2020

Antipsychotic drugs are utilized for far more than the treatment of psychosis in schizophrenia, their first indication. They now find wide use in a variety of psychotic disorders, mood disorders, developmental disorders, and drug-induced disorders. The classification of drugs as typical or atypical is based on their differences in extra-pyramidal side effects (EPS). This chapter emphasizes the greater diversity, efficacy, and safety of the atypical drugs, and the risk of tardive dyskinesia of the typical drugs. The atypical drug action may produce improvement in cognitive function and negative symptoms, as well as psychosis and mood in some patients. This diversity includes atypical drugs which produce minimal weight gain. Long-acting injectable formulations are recommended for non-adherent patients. The exceptional ability of clozapine to reduce the risk for suicide and to decrease mortality in schizophrenia is discussed. Anticholinergic and other drugs to treat EPS are also discussed.
Epidemiology of mood disorders
Authors: Kessing Lars Vedel
Published: March 2020

Unipolar depressive disorder and bipolar disorder are common mental diseases that impose a very high societal burden in terms of morbidity, mortality, lost productivity, and costs. The 1-year prevalence of bipolar disorder is 1–2%, while the 1-year prevalence of depressive disorder is 3–6%. Mean age at onset is in the early to mid twenties for bipolar disorder and around 30 years of age for depressive disorder. The risk of recurrence of episodes after a first depression or manic episode is high, especially for bipolar disorder, and approximately 1% of patients convert from depressive disorder to bipolar disorder per year. Comorbidity with anxiety disorders, alcohol and drug dependence, and personality disorders is high. Both disorders are associated with long-term deficits in social, functional, and cognitive outcomes, and life expectancy is decreased by approximately 10 years, emphasizing the need for future studies on early intervention.
Genetics of bipolar disorder
Authors: McMahon Francis J. , Detera-Wadleigh Sevilla
Published: March 2020

Bipolar disorder represents one of the most highly heritable group of common psychiatric disorders, but the complex genetic basis of these disorders has only recently begun to reveal itself. This chapter reviews the genetic epidemiology, molecular genetics, and genetic modelling studies of bipolar disorder. The chapter concludes with a glimpse of anticipated developments of relevance to clinical care and anticipates some future research directions.
Neuroimaging of bipolar disorder
Authors: Phillips Mary L , Drevets Wayne C
Published: March 2020

This chapter discusses findings from recent major neuroimaging studies of bipolar disorder to provide a better understanding of larger-scale neural circuitry, neurotransmitter concentration, bioenergetic process, and protein marker abnormalities in the disorder. The chapter also reviews findings from newer areas of neuroimaging research, including studies comparing bipolar disorder with other major psychiatric disorders, multimodal neuroimaging studies, studies of youth with, and youth at risk for, the disorder, and studies using machine-learning pattern recognition techniques. These studies are paving the way for identification of robust and objective neural biomarkers of bipolar disorder that can ultimately have clinical utility.
Basic mechanisms of, and treatment targets for, stress-related disorders
Authors: McEwen Bruce S.
Published: March 2020

The response to the social and physical environment involves two-way communication between the brain and the body and epigenetic adaptation (‘allostasis’) via mediators of the cardiovascular, immune, metabolic, neuroendocrine, and neural mechanisms. Chronic stress causes wear and tear on the brain and body (‘allostatic load and overload’), reflecting also the impact of health-damaging behaviours and lasting effects of early life experiences interacting with genetic predispositions. Hormonal and other mediators of allostasis promote adaptation in the short run but cause allostatic load/overload when they are overused or dysregulated. The brain is key because it determines what is threatening and the physiological and behavioural responses, while showing structural remodelling that affects its function. Besides pharmaceuticals, there are ‘top–down’ interventions, like physical activity, that engage ‘the wisdom of the body’ to change itself, as well as the impact of policies of government and business that encourage individuals to manage their own lives and promote increased ‘healthspan’.
Recovered memories and false memories
Authors: Davis Deborah , Loftus Elizabeth F.
Published: March 2020

This chapter provides a brief review of the history and elements of the controversy surrounding the reality of repression and recovery of memories of sexual abuse and other traumatic events. The main body of the chapter concerns the mechanisms through which false memories of such events can be formed. These include the importance of culturally prevalent misconceptions regarding the operation of memory, suggestion in the context of therapy and other social interactions, prominent books promoting misconceptions regarding memory and abuse, and processes that can alter or create elements of memory (belief, sensory images, and the criteria by which these are judged as memories or not). Suggestions are offered for how claims of repressed and recovered memories should be treated in court and for practices with potential for memory distortion that should be avoided.
Treatment of anxiety disorders
Authors: Baldwin David S. , Huneke Nathan T.M
Published: March 2020

The personal and societal burden associated with anxiety disorders is considerable, but many individuals who might benefit from treatment are not recognized. Recognition relies on awareness of psychological and physical symptoms common to all anxiety disorders, and accurate diagnosis on identifying specific features of particular disorders. The need for treatment is determined by the severity and persistence of symptoms, the impact of symptoms on everyday life, the presence of coexisting depressive symptoms, and other features such as response to previous treatment approaches. Patient characteristics and patient and doctor preferences influence the choice of treatment. There is much overlap between anxiety disorders in evidence-based and effective therapies (such as the prescription of a selective serotonin reuptake inhibitor or a course of individual cognitive behavioural therapy), but there are also important differences, so it helps to be familiar with the characteristic features and evidence base for each condition.
Management and treatment of obsessive–compulsive disorder
Authors: Fineberg Naomi A. , Drummond Lynne M. , Reid Jemma , Cinosi Eduardo , Carmi Lior , Mpavaenda Davis N.
Published: March 2020

This chapter reviews the evidence-based treatment of obsessive–compulsive disorder (OCD) across the lifespan. Cognitive behavioural therapies involving exposure and response prevention and pharmacotherapy with selective serotonin reuptake inhibitors (SSRIs) or clomipramine represent well-established treatments, though a substantial proportion of patients fail to respond. Although there are grounds to believe combining psychological and pharmacological treatments may be more effective than monotherapy, the evidence supporting this approach remains inconclusive. Moreover, a substantial proportion of patients go on to relapse. Pharmacotherapy can protect against relapse as long as it is sustained. Of the existing strategies for resistant OCD, drug combination with an adjunctive dopamine antagonist shows the strongest evidence of efficacy. Other less well-evidenced psychological, pharmacological, and somatic treatment strategies are also described, including advanced surgical procedures for severe, highly refractory OCD.
Basic mechanisms and potential for treatment of weight and eating disorders
Authors: Hebebrand Johannes , Antel Jochen , Herpertz-Dahlmann Beate
Published: March 2020

Eating and weight disorders frequently persist over time despite extensive therapeutic efforts. Both high dropout and lost-to-follow-up rates observed in randomized controlled trials indicate that many patients are not satisfied by current treatment options. Particularly, obesity-related research has underscored the multitude and complexity of aetiological factors involved in body weight regulation. Multiple lines of evidence point to an intertwining of the regulation of energy intake and expenditure with other somatic and mental functions. The elucidation of monogenic forms of obesity has led to the identification of drug targets, which may prove helpful for the treatment of eating and weight disorders. This chapter discusses potential treatment strategies for these disorders, based on our greatly improved understanding of the underlying neurobiological mechanisms and the function of the microbiome in body weight regulation.
Genetics of feeding and eating disorders
Authors: Hübel Christopher , Bulik Cynthia M. , Breen Gerome
Published: March 2020

Eating disorders are serious psychiatric illnesses that are associated with a broad range of somatic and psychiatric comorbidities, high disability-adjusted life years, and premature mortality. As candidate gene and linkage studies are increasingly out of favour and have been dealt with elsewhere, this chapter focuses on reviewing modern and robust genetic findings that exist for eating disorders. Eating disorders are moderately to highly heritable conditions, with additional environmental risk factors that may (or may not) interact with genetic risk. Similar to the picture in other psychiatric disorders, the evidence strongly suggests that eating disorders are highly complex (‘polygenic’) and that large-scale genome-wide association studies that include tens of thousands of cases will ultimately be required. This will lead to substantial and potentially revolutionary new understanding of the aetiopathology of eating disorders. The available data are already suggesting a combined metabolic and psychiatric genetic aetiology of eating disorders.
Aetiology and management of obesity
Authors: Hartmann-Boyce Jamie , Astbury Nerys M. , Jebb Susan A.
Published: March 2020

In 2014, almost 2 billion adults had overweight or obesity, and prevalence continues to increase. The fundamental cause of obesity is an imbalance between energy expenditure and intake, but determinants of these behaviours are complex. Obesity is one of the most important preventable causes of morbidity and mortality, and its control is one of the most pressing issues facing modern health care systems. Primary prevention is vital, but many of the health risks can be mitigated by weight loss. There has been considerable progress in weight management interventions for adults, including behavioural programmes, pharmacotherapy, and surgeries, but management in children and adolescents remains more challenging. Weight regain post-intervention is common, and obesity needs to be managed as a chronic, relapsing condition with individual-level interventions offered on repeated occasions. Population-level interventions to curb the environmental drivers of obesity are important for primary prevention and to reinforce individual-level actions for weight control.
Elimination disorders in children and adolescents
Authors: von Gontard Alexander
Published: March 2020

Elimination disorders (EDs) encompass faecal incontinence or encopresis, daytime urinary incontinence, and nocturnal enuresis. Many different subtypes can be identified. EDs are common disorders in childhood, associated with emotional distress and a higher rate of comorbid psychiatric disorders such as attention-deficit/hyperactivity disorder. These have to be addressed separately. Genetic and environmental factors play a role in the aetiologies of EDs. Medical causes have to be ruled out, but most EDs are functional, that is, non-organic. Assessment is non-invasive and clinically based in most cases. Treatment is symptom-oriented, with the goal of complete continence. The most effective treatment is primarily by urotherapy, cognitive behavioural therapy, and medication. As each subtype of ED requires a specific treatment approach, an exact diagnosis is essential. International guidelines are available to ensure optimal care for children and adolescents with EDs.
Epidemiology of sleep–wake and primary prevention of its disorders
Authors: Keller Lena Katharina , Winnebeck Eva C. , Roenneberg Till
Published: March 2020

This chapter summarizes epidemiological insights into sleep and wake behaviour and covers the limited knowledge about its disorders, with special emphasis on psychiatry. The chapter systematically refers to the interdependencies of four different aspects in both sleep and wake: timing, duration, structure, and quality. It provides an overview of the current methods used in the field for studying this behaviour and predicts that long-term actimetry monitoring in everyday life will revolutionize research into both sleep and the circadian clock. The chapter argues that a stronger alliance between sleep research and circadian biology will help to better understand the different aetiologies of sleep disorders, as well as the relationships between sleep and disease. It is predicted that strengthening our consideration of sleep’s circadian regulation versus its societal constraints—together with improved light environments—will ameliorate many sleep problems. There is also a need to improve public education about sleep and the circadian clock to increase self-awareness of sleep, activity, and light behaviour on an individual level to prevent false self-diagnoses due to misconceptions about sleep.
Multimodal imaging of sleep–wake disorders
Authors: Moretto Umberto , Smith Dylan , Dell’Osso Liliana , Dang-Vu Thien Thanh
Published: March 2020

While the neuroscience of sleep has traditionally been studied using electroencephalography (EEG), newer technologies have allowed for an enriched understanding of the brain’s ongoing activity during transitions into sleep, as well as during the distinct stages of sleep observed in humans. Neuroimaging techniques such as magnetic resonance imaging (MRI), functional MRI (fMRI), voxel-based morphometry (VBM), diffusion tensor imaging (DTI), magnetic resonance spectroscopy (MRS), positron emission tomography (PET), and single-photon emission computed tomography (SPECT) allow researchers a window into the brain during both waking and sleep. As an extension, deviations from brain activity patterns observed in healthy good sleepers give clues to the specific brain abnormalities associated with disorders of sleep such as insomnia. This chapter will provide a selected overview of neuroimaging studies in sleep and sleep disorders.
Basic mechanisms of, and treatment planning/targets for, personality disorders
Authors: Saunders Kate E. A. , Pearce Steve
Published: March 2020

Personality disorders are a divergent group of diagnoses which are pervasive in nature and, until recent years, were thought to be treatment-resistant. While the majority of current treatments have evolved on the basis of psychoanalytic and behavioural theories of personality development, there is an emerging understanding of the underlying neurobiology. Current neuroscientific evidence, supported by the theoretical underpinnings of successful psychotherapeutic interventions, converges on social functioning and mood regulation as key treatment targets in personality disorder, and specifically in borderline personality disorder.
Genetics of personality disorders
Authors: Cloninger C. Robert
Published: March 2020

Family, twin, and adoption studies have shown that personality disorders are moderately heritable, but most of the variability is the result of non-additive interactions among many genetic variants and environmental events acting in concert. Consequently, the pathway from genotype to phenotype is complex—individuals with the same genotype may have different features of personality disorder, or none (multifinality, also called pleiotropy), and individuals with different genotypes may have the same personality disorder (equifinality, also called heterogeneity). The same genetic and environmental variants cause normal and abnormal personality, so personality disorders are the result of quantitative trait variation and are not discrete disease entities. Human character traits, such as self-directedness and co-operativeness, allow people to self-regulate their emotional drives, and recent person-centred genome-wide association studies have revealed that these character traits are strongly influenced by regulatory gene variants, such as long non-coding RNAs, that influence adaptive functioning and neuroplasticity by epigenetic mechanisms.
Imaging of personality disorders
Authors: Paret Christian , Schmahl Christian
Published: March 2020

Altered processing of emotion, cognition, social interactions, and behavioural responding is characteristic for personality disorders. Neuroimaging has contributed to a better understanding of biological markers of inflexible and maladaptive behaviours prevalent in personality disorders. This chapter summarizes results from magnetic resonance imaging and electroencephalography studies, with a focus on research in borderline personality disorder (BPD). Knowledge on neural processes underlying emotion processing and emotion regulation has significantly advanced. Overall, findings corroborate dysfunctions in limbic–prefrontal networks, emphasizing hyper-responsiveness of the amygdala and a lack of prefrontal control. Neuroimaging studies addressed several domains of cognitive functions in BPD and shed light on the processing of social information in the brain. Though profound achievements have been made, comprehensive neurobiological models addressing behavioural dysregulation, impulsivity, and abnormal social interaction in BPD are still pending.
Treatment and management of personality disorder
Authors: Newton-Howes Giles , Mulder Roger
Published: March 2020

The management of personality disorders remains a complex and challenging area, in which significant advances have been made to our understanding over the last two decades. As an increasing understanding of the diagnosis of personality disorder is recognized, our ability to understand what interventions could be of value continues to develop. The diagnosis of borderline personality disorder is where the most significant understanding has occurred. It is now clear that these disorders can be recognized early in development and treatment should be primarily psychological. Cognitive, dynamic, and educational approaches have been trialled and found to be effective. Further, pharmacotherapy is best considered for short-term, symptom-focused use, as opposed to long-term therapy. The evidence suggests dopamine antagonists and mood stabilizers are the drugs of choice. Identifying the needs and developing strategies to meet these provide greater benefit than focusing on risk.
Factitious disorder and malingering
Authors: Merten Thomas , Merckelbach Harald
Published: March 2020

Factitious disorder and malingering are two forms of abnormal illness behaviour in which mental or somatic symptoms are deliberately fabricated or grossly exaggerated or otherwise grossly misrepresented. They are forms of other-deceit, with the person in question assumed to be fully aware of this deceit. The central distinguishing feature of both is that factitious disorder is commonly thought to be motivated by internal incentives (primary gain: medical treatment, assuming the sick role), while malingering is directed towards an external goal (secondary gain, for example monetary compensation, sick leave). The utility of distinguishing between the two forms of feigning has long been questioned. Similarly, it must be questioned why factitious disorder is apprehended as a mental disorder in its own right. Neither the Diagnostic and Statistical Manual of Mental Disorders (DSM) nor the International Classification of Diseases (ICD) contains useful diagnostic guidelines for reliably diagnosing feigned illness presentations; in particular, several decades of malingering research and conceptual developments have found no repercussion there.
Functional neurological symptom disorder (conversion disorder)
Authors: Stone Jon , Sharpe Michael
Published: March 2020

Conversion disorder (now also called functional neurological symptom disorder) describes symptoms (of motor and sensory dysfunction such as limb weakness, tremor, visual loss, with or without ‘blackouts’), which can be positively identified as being inconsistent with neurological disease. The disorder is common in neurological services and frequently seen by psychiatrists working in such settings. It is often associated with chronic severe disability. The diagnosis previously hinged on the neurologist’s demonstration of the lack of disease and the psychiatrist’s hypothesis of a ‘conversion’ of stress into a physical symptom. It is now based on positive findings on neurological assessment supplemented by a psychiatric assessment to confirm the diagnosis. Comorbid anxiety and depression disorders are common. Treatment is multi-disciplinary. Explanation of the condition to the patient is a crucial initial step supplemented, where necessary, by psychological treatment (especially for dissociative or non-epileptic attacks) and physiotherapy for functional motor symptoms. The prognosis without treatment is poor once the disability is established.
Health economic analysis of service provision
Authors: Simon Judit
Published: March 2020

Resources available in the health care system are limited and are exceeded by needs. Public health and long-term care expenditures have been rising steadily, relative to national income, for several decades. Currently, the costs of mental ill-health account for up to 14% of health spending in Organisation for Economic Co-operation and Development (OECD) countries, and this proportion is also expected to rise further. Decisions on how best to allocate scarce resources are therefore becoming increasingly prominent among health policy-makers with specific relevance to mental health services. This chapter summarizes the health economic methods used to inform the key questions of decision-makers in health care related to efficiency and equity. It provides an explanation of the underlying economic and analytical frameworks and gives a summary of the different techniques of health economic analyses, supported by a selection of recent relevant published examples from the mental health field.
Oxford Handbook of Medical Statistics
Authors: Peacock Janet L. , Peacock Phil J.
Published: March 2020

A good understanding of medical statistics is essential to evaluate medical research and to choose appropriate ways of implementing findings in clinical practice. The Oxford Handbook of Medical Statistics, second edition, has been written to provide doctors and medical students with a comprehensive yet concise account of this often difficult subject. Described by readers as a ‘statistical Bible’, this new edition maintains the accessibility and thoroughness of the original, and includes comprehensive updates including new sections on transitional medicine, cluster designs, and modern statistical packages. The handbook promotes understanding and interpretation of statistical methods across a wide range of topics, from study design and sample size considerations, through t and chi-squared tests, to complex multifactorial analyses, all using examples from published research. References and further reading are included, to allow deeper understanding on specific topics. Featuring a new chapter on how to use this book in different medical contexts, the Oxford Handbook of Medical Statistics helps readers to conduct their own research and critically appraise others' work.
Research design
Authors: Peacock Janet L. , Peacock Philip J.
Published: March 2020

This chapter describes the main features of the design of interventional and observational studies and the differences and similarities between research and audit. It discusses when a sample size calculation is needed, describes the main principles of the calculations, and outlines the steps involved in preparing a study protocol. Most sections are illustrated with examples and particular attention is given to the statistical issues that arise in designing and appraising research.
Collecting and handling data
Authors: Peacock Janet L. , Peacock Philip J.
Published: March 2020

This chapter gives suggestions for designing questions and questionnaires, and discusses the consequences of different question designs on the resulting statistical analyses. It also discusses different methods of data entry and handling datasets in computer packages. The importance of checking for errors in the data is highlighted with suggestions of how to do this. Finally, the role of data monitoring committees in research trials is discussed, along with the implications of ending trials early. Examples are provided throughout the chapter.
Presenting research findings
Authors: Peacock Janet L. , Peacock Philip J.
Published: March 2020

This chapter discusses the different formats for disseminating research findings and the different sections of a research paper or report. It also describes the best ways to present statistical results and discusses guidelines for research articles. Examples are given throughout.
Choosing and using statistical software for analysing data
Authors: Peacock Janet L. , Peacock Philip J.
Published: March 2020

This chapter describes the main features of statistics packages, what they do, and what they do not do. It describes how users interact with packages, how to transfer data between packages, and how to decide which package to use. There are many statistical analysis computer packages and programs on the market and this chapter does not provide a review of what is available. Instead, it discusses the main issues that drive the choice of package to use. To illustrate, a few packages that the authors know well are briefly described.
Summarizing data
Authors: Peacock Janet L. , Peacock Philip J.
Published: March 2020

This chapter describes types of quantitative and categorical data and shows how these different types of data can be summarized numerically and in graphs. It gives worked examples of how to calculate the mean, median, standard deviation, and interquartile range, and gives examples of displaying data in graphs.
Probability and distributions
Authors: Peacock Janet L. , Peacock Philip J.
Published: March 2020

Probability and probability distributions play a central part in medical statistics. This chapter defines what is meant by probability and describes the rules by which probabilities are combined. It then describes how the use of probability leads to the concept of a probability distribution and shows how these distributions are used in medical statistics. Examples are given of the use of key distributions: the Normal distribution, the binomial distribution, and the Poisson distribution.
Meta-analysis
Authors: Peacock Janet L. , Peacock Philip J.
Published: March 2020

This chapter describes the statistical issues involved in performing meta-analyses. It discusses the sources and effects of publication bias and considers ways of correcting for it. It also discusses statistical and clinical heterogeneity and considers how these can be addressed in meta-analyses. Finally, it describes individual patient meta-analysis. Throughout, the chapter includes both trials and observational studies, discussing the challenges that each study design brings and giving examples.
Bayesian statistics
Authors: Peacock Janet L. , Peacock Philip J.
Published: March 2020

This chapter describes the Bayesian approach to statistical analysis in contrast to the frequentist approach. It discusses how clinicians often use a Bayesian approach in interpreting clinical findings and forming management plans. It describes how Bayesian methods work including a description of prior and posterior distributions. The chapter outlines the role and choice of prior distributions and how they are combined with the data collected to provide an updated estimate of the unknown quantity being studied. It includes examples of the use of Bayesian methods in medicine, and discusses the pros and cons of the Bayesian approach compared to the frequentist approach. Finally, guidance is given on how to read and interpret Bayesian analyses in the medical literature.
Glossary of terms
Authors: Peacock Janet L. , Peacock Philip J.
Published: March 2020

This chapter contains a glossary of key terms used in the book, in alphabetical order.
L
Authors: Ainsworth Sean
Published: March 2020

This chapter presents information on neonatal drugs that begin with L, including use, pharmacology, adverse effects, fetal and infant implications of maternal treatment, treatment, and supply of Labetalol hydrochloride, Lactoferrin, Lamivudine, Lamotrigine, Lansoprazole, Levetiracetam, Levosimendan, Levothyroxine sodium, Lidocaine = Lignocaine (former BAN), Linezolid, Lipid emulsions for parenteral nutrition, Loperamide, Lopinavir with ritonavir, Lorazepam, and Low-molecular-weight heparins and other anticoagulants
N
Authors: Ainsworth Sean
Published: March 2020

This chapter presents information on neonatal drugs that begin with N, including use, pharmacology, adverse effects, fetal and infant implications of maternal treatment, treatment, and supply of Naloxone, Neostigmine (and pyridostigmine), Nevirapine, Nifedipine, Nitazoxanide, Nitisinone, Nitric oxide, Nitrofurantoin, Nitrous oxide, Noradrenaline = Norepinephrine (rINN), and Nystatin
Q
Authors: Ainsworth Sean
Published: March 2020

This chapter presents information on neonatal drugs that begin with Q, including use, pharmacology, adverse effects, fetal and infant implications of maternal treatment, treatment, and supply of Quinine
R
Authors: Ainsworth Sean
Published: March 2020

This chapter presents information on neonatal drugs that begin with R, including use, pharmacology, adverse effects, fetal and infant implications of maternal treatment, treatment, and supply of Radiological contrast media, Raltegravir, Ranitidine, Recombinant human granulocyte colony-stimulating factors (rhG-CSF), Remifentanil, Rhesus (D) immunoglobulin, Ribavirin = Tribavirin (former BAN), Rifampicin = Rifampin (USAN), Rocuronium, Rotavirus vaccines, and Rubella vaccine
T
Authors: Ainsworth Sean
Published: March 2020

This chapter presents information on neonatal drugs that begin with T, including use, pharmacology, adverse effects, fetal and infant implications of maternal treatment, treatment, and supply of Teicoplanin, Tenofovir, Tetracaine = Amethocaine (former BAN), Tetracosactide = Tetracosactrin (former BAN), Tetracycline, Thiopental sodium = Thiopentone sodium (former BAN), Tobramycin, Topiramate, Tramadol, Tranexamic acid, Trimethoprim, and Trometamol = Tromethamine (USAN)
U
Authors: Ainsworth Sean
Published: March 2020

This chapter presents information on neonatal drugs that begin with U, including use, pharmacology, adverse effects, fetal and infant implications of maternal treatment, treatment, and supply of Ubidecarenone (coenzyme Q10), Urokinase, and Ursodeoxycholic acid = Ursodiol (USAN)
V
Authors: Ainsworth Sean
Published: March 2020

This chapter presents information on neonatal drugs that begin with V, including use, pharmacology, adverse effects, fetal and infant implications of maternal treatment, treatment, and supply of Vancomycin, Varicella-zoster immunoglobulin and vaccine, Vasopressin, desmopressin, and terlipressin, Vigabatrin, Vitamin A (retinol), Vitamin B12 (hydroxocobalamin), Vitamin D (special formulations), Vitamin D (standard formulations), Vitamin E (alpha tocopherol), Vitamin K1 = phytomenadione (rINN), phytonadione (USAP), and Vitamins (multi-vitamins)
Z
Authors: Ainsworth Sean
Published: March 2020

This chapter presents information on neonatal drugs that begin with Z, including use, pharmacology, adverse effects, fetal and infant implications of maternal treatment, treatment, and supply of Zidovudine (azidothymidine), and Zinc
Maternal medication and its effect on the baby
Authors: Ainsworth Sean
Published: March 2020

All too often the pregnant or breastfeeding mother is told that she cannot receive a drug because the manufacturer has advised against its use. Such information is usually derived from the Summary of Product Characteristics and reflects a lack of information of such use during the early stages of drug development and licensing. These statements are always cautious, seldom very informative, and often merely designed to meet the minimum requirement laid down by the licensing authority. While there are a small number of drugs whose use during pregnancy and lactation is extremely unwise, for most drugs it is more a matter of balancing the advantages and the disadvantages. Information from pregnancy and lactation databases increasingly supplements the information from animal teratogenicity and toxicology studies. Prescribers must consider both disease and drug characteristics when making decisions on medication use during both pregnancy and lactation. They can then use this information to balance the risks of fetal or neonatal exposure against the potential benefits of maternal treatment and the risks of untreated disease. This section allows the reader to quickly look up such risks and, through the references, examine the primary literature to help the mother make an informed choice.
Monte Carlo simulations of black hole mergers in AGN discs: Low χeff mergers and predictions for LIGO
Authors: McKernan B , Ford K E S , O’Shaugnessy R , Wysocki D
Published: March 2020

Accretion discs around supermassive black holes are promising sites for stellar mass black hole mergers detectable with LIGO. Here we present the results of Monte Carlo simulations of black hole mergers within 1-d AGN disc models. For the spin distribution in the disc bulk, key findings are: (1) The distribution of χeff is naturally centred around $\tilde{\chi }_{\rm eff} \approx 0.0$, (2) the width of the χeff distribution is narrow for low natal spins. For the mass distribution in the disc bulk, key findings are: (3) mass ratios $\tilde{q} \sim 0.5\!-\!0.7$, (4) the maximum merger mass in the bulk is $\sim 100\!-\!200\, \mathrm{M}_{\odot }$, (5) $\sim 1{{\ \rm per\ cent}}$ of bulk mergers involve BH $\gt 50\, \mathrm{M}_{\odot }$ with (6) $\simeq 80{{\ \rm per\ cent}}$ of bulk mergers are pairs of first generation BH. Additionally, mergers at a migration trap grow an IMBH with typical merger mass ratios $\tilde{q}\sim 0.1$. Ongoing LIGO non-detections of black holes $\gt 10^{2}\, \mathrm{M}_{\odot }$ puts strong limits on the presence of migration traps in AGN discs (and therefore AGN disc density and structure) as well as median AGN disc lifetime. The highest merger rate occurs for this channel if AGN discs are relatively short-lived (≤1 Myr) so multiple AGN episodes can happen per Galactic nucleus in a Hubble time.
Helium and nitrogen enrichment in massive main-sequence stars: mechanisms and implications for the origin of WNL stars
Authors: Roy Arpita , Sutherland Ralph S , Krumholz Mark R , Heger Alexander , Dopita Michael A
Published: March 2020

The evolutionary paths taken by massive stars with M ≳ 60 M⊙ remain substantially uncertain. They begin their lives as main-sequence (MS) O stars. Depending on their masses, rotation rates, and metallicities, they can then encounter a wide range of evolutionary states with an equally broad set of possible surface compositions and spectral classifications. We present a new grid of calculations for the evolution of such stars that covers a broad range in mass, M/M⊙ = 60–150, rotation rate, $v/v_{\rm crit} = 0$–0.6, metallicity, [Fe/H] = −4 to 0, and α-element enhancement, [α/Fe] = 0–0.4. We show that rotating stars undergo rotationally induced dredge-up of nucleosynthetic products, mostly He and N, to their surfaces while still on the MS. Non-rotating metal-rich stars also reveal the products of nucleosynthesis on their surfaces because even modest amounts of mass-loss expose their ‘fossil’ convective cores: regions that are no longer convective, but were part of the convective core at an early stage in the star’s evolution. Thus, surface enhancement of He and N is expected for rotating stars at all metallicities, and for non-rotating stars if they are relatively metal-rich. We calculate a stellar atmosphere for a representative model from our grid, properly accounting for He and N enhancement, and show that the resulting spectrum provides a good match to observed WNL stars, strongly suggesting that the physical mechanisms we have identified are the ultimate cause of the WNL phase.