bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cultural contexts and constructions of recovery
Authors: Adeponle Ademola , Whitley Rob , Kirmayer Laurence J. 
Published: May 2013

AbstractThis chapter examines the social and cultural roots and implications of current concepts of recovery. Consistent with biomedical notions of illness and disease, psychiatry has tended to frame “recovery” largely in terms of outcomes, as “recovery from illness”. However, during the last decade the term “recovery” has come to refer to a social movement promoting a reorientation in psychiatric care, toward ensuring that individuals can live a full life in their communities. Along with this reorientation, recovery is increasingly conceived of as a process, rather than an outcome, with individuals described as “being in recovery” rather than as “recovering from” an affliction. The new recovery “movement”, with its roots in civil rights and independent living movements, arose in part as a reaction to perceived attitudes of pessimism and paternalism inherent in conventional psychiatric care. It envisions for individuals with mental illness a reassertion of their rights to a dignified and meaningful life in the community and a renewed sense of agency, with an active say in the direction of their own healthcare. Although sometimes framed in the universalistic language of human rights, recovery is rooted in specific cultural concepts of self and personhood. The consumer-oriented recovery model, which is popular in the USA, builds on a Euro-American individualistic and egocentric concept of the person. However, in other cultures, sociocentric, ecocentric, or cosmocentric conceptions of personhood may have more salience. These differing cultural concepts of the person influence the trajectories of illness, modes of adaptation, response to interventions, and definitions of positive outcome. In particular, cultural notions of the person's connection to family, community, and spirituality play a key role in local notions of recovery. This will be illustrated with examples from qualitative research with African-Americans in the USA, indigenous peoples in Canada, and patients in Nigeria. Understanding the cultural and historical roots of recovery provides a framework for considering the relevance of recovery for diverse cultural groups, both within North American and European societies and in other parts of the world.
Glutamate Receptors in Epilepsy
Authors: Bianchi Riccardo , Wong Robert K. S. , Merlin Lisa R. 
Published: May 2013

Abstract
In the early 1990s, the epileptogenic potential of metabotropic glutamate receptor (mGluR) activation in the hippocampus was first suggested by data using the then newly developed broad- spectrum mGluR agonist (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (ACPD).1 These studies revealed that mGluR activation had the potent ability to recruit the hippocampal network to express robust synchronized discharges. These synchronized bursts had features suggestive of typical seizure discharges in that (1) their length was on the order of seconds and (2) they were comprised of an intrinsic oscillatory series of discharges that began at a high frequency and gradually slowed. And indeed, work in other labs confirmed that ACPD application does elicit seizures in the intact organism.2 A hypothesis was developed proposing that the group I mGluRs, which are predominantly localized to the edges of synapses (perisynaptic),3 were likely to be activated at times of intense glutamate release, and this could result in the expression of acute seizures such as the impact seizure that occurs acutely in the setting of head trauma. However, subsequent studies using the selective group I mGluR agonist (S)-3,5-dihydroxyphenylglycine (DHPG) revealed a potential additional consequence of group I mGluR activation: long- lasting changes in network excitability.4
Plasticity of Glutamate Synaptic Mechanisms
Authors: Nadler J. Victor 
Published: May 2013

Abstract
Epilepsy may be defined as a disorder of brain function characterized by the repeated and unpredictable occurrence of seizures. Seizures involve the disordered, rhythmic, and synchronous firing of central nervous system (CNS) neuron populations. Seizures originate in neuronal populations capable of bursting, develop because of an imbalance between neuronal excitation and inhibition, and are characterized by high-frequency firing associated with membrane depolarization. Neuronal excitation and inhibition may become unbalanced in many different ways. This chapter focuses on the contribution to seizures of glutamate synaptic plasticity, both anatomical plasticity that creates new excitatory synapses and functional plasticity that enhances the efficacy either of excitatory synapses or of glutamate itself. Observations made with human tissue are emphasized. Glutamate is the principal excitatory neurotransmitter in mammals. About 60%–70% of all synapses in the CNS appear to be glutamate synapses (see Fig. 12–1). Glutamate also serves as the principal neurotransmitter utilized by sensory neurons. Autonomic neurons and motoneurons are about the only excitatory neurons in mammals that utilize a transmitter other than glutamate. Thus, the formation of enhanced or novel glutamate circuits, enhanced excitatory transmission, and/or an excess of glutamate itself could disrupt the balance of excitation and inhibition leading to the occurrence of seizures.
Fast Oscillations and Synchronization Examined with In Vitro Models of Epileptogenesis
Authors: Traub Roger D. , Whittington Miles A. , Cunningham Mark O. 
Published: May 2013

Abstract
For many years, interictal spikes, recorded in a patient's electroencephalogram (EEG), were considered to be a primary indicator that the patient might indeed have epilepsy and that the patient's seizures (when they occurred) were likely to begin in the vicinity of the interictal spike generator. That interictal spikes could often be recorded at the scalp, without the necessity of invasive recording procedures, contributed to their clinical usefulness. A question of continuing importance to basic epilepsy research was naturally this: what factors determine whether “epileptogenic tissue” will produce interictal spikes,1 unequivocal seizure activity, or something intermediate?
Fever, Febrile Seizures, and Epileptogenesis
Authors: Dubé Céline M. , McClelland Shawn , Choy ManKin , Brewster Amy L. , Noam Yoav , Baram Tallie Z. 
Published: May 2013

Abstract
Febrile seizures (FS) are the most common type of convulsions in infants and young children, occurring in 2%–6% of children.1,2 They are defined as seizures arising during fever, not caused by an infection of the central nervous system. However, their definition does not exclude children with preexisting neurological deficits, a fact that might confound studies on the outcome of these seizures. Although there is limited evidence for adverse outcomes of simple (defined as short, with no focal motor phenomena) FS on the immature brain, complex FS, particularly long-duration FS or febrile status epilepticus (defined as seizures lasting for more than 30 min), have been associated with subsequent limbic epilepsy, as indicated by both prospective and retrospective studies as well as by recent data in animal models.3–14 Some investigators have suspected that long-duration FS might result in cognitive defects in a subset of children.15–17 Understanding the basic mechanisms of FS, and the potential epileptogenesis that follows them, requires animal models that enable direct examination of the causal mechanisms for the generation and consequences of these seizures. The mechanisms by which fever leads to FS, the outcome of FS measured as the risk of epilepsy, the properties of FS associated with limbic epilepsy, and the mechanisms of epileptogenesis are discussed in the following sections.
The Time Course and Circuit Mechanisms of Acquired Epileptogenesis
Authors: Dudek F. Edward , Staley Kevin J. 
Published: May 2013

Abstract
In order to develop and test possible therapeutic strategies for preventing or suppressing epileptogenesis, the temporal features of acquired epilepsy and its underlying mechanisms must be understood. These temporal features include the frequency, duration, and cortical extent of spontaneous seizures; this review focuses primarily on seizure frequency. Traumatic brain injury, stroke, status epilepticus, and infection/inflammation are some of the major causes of acquired epilepsy. The spontaneous recurrent epileptic seizures of acquired epilepsy usually occur after a latent period following the injury, and in at least some patients, the epilepsy is progressive (i.e., the seizures become more frequent and severe). Nearly all patients receive antiepileptic drugs (AEDs) after one or a few clinical seizures. Therefore, quantitative analyses of the temporal features of acquired epileptogenesis, independent of the effects of AEDs, cannot be studied in humans. Animal models of acquired epilepsy can circumvent this problem. The research summarized here analyzed the development of spontaneous recurrent seizures (1) in kainate-treated rats,1 an animal model of temporal lobe epilepsy, and (2) in rats subjected to hypoxic-ischemic brain damage at postnatal day 7, a model of perinatal stroke.2–4
Perturbations of Dendritic Excitability in Epilepsy
Authors: Tang Cha-Min , Thompson Scott M. 
Published: May 2013

Abstract
The dendrite is where thousands of excitatory and inhibitory synaptic inputs are received by the neuron. But rather than just being a simple antenna, the dendrite is also the location where these inputs actively interact with intrinsic conductances. The interactions are complex and are still incompletely understood. The synaptic inputs are distributed in time and space, and each of the many intrinsic dendritic conductances is also distributed in its own unique spatial pattern. The interactions lead to signal transformations whose significance may be best appreciated in terms of elementary steps in signal processing and computation. Under pathological conditions, changes to these interactions may result in aberrant excitability and contribute to neurological disease. Rather than compiling a list of dendritic conductances and their linkages with epilepsy, which is done in other chapters of this book, the purpose of this chapter is to integrate these results, with an emphasis on how perturbations of the elementary steps in dendritic integration affect the way neurons process their inputs and promote aberrant neuronal excitability.
Temporal Lobe Epilepsy and the BDNF Receptor, TrkB
Authors: McNamara James O. , Scharfman Helen E. 
Published: May 2013

Abstract
Actions of estrogen and progesterone have been used to explain the changes in seizure frequency or severity in women with catamenial epilepsy. An alternative hypothesis is that BDNF is responsible, because estrogen causes an increase in BDNF expression that can have both acute effects on excitability and delayed, indirect effects by changing GABAergic transmission and GABAA receptors. Allopregnanolone may hold many of the excitatory effects in check during the luteal phase, but two phases of the cycle may be unprotected, the periovulatory and perimenstrual phases. This hypothesis helps explain why progesterone therapy may not always be efficacious in catamenial epilepsy and suggests that control of BDNF would be a logical complementary strategy.
GABAA Receptor Plasticity in Alcohol Withdrawal
Authors: Olsen Richard W. , Spigelman Igor 
Published: May 2013

Abstract
Alcohol, the fruit of the vine and the braumeister's ware, has been one of the most popular drugs in the world throughout history and one of the most abused. The development of dependence after chronic use of ethanol (EtOH) depends on two parallel effects of the drug on the brain each time it is used: stimulation of the reward pathway and subsequent triggering of a small but significant withdrawal. There is rebound hyperexcitability following the initial action of EtOH as a central nervous system (CNS) depressant and triggering of some adaptive process, that is, molecular changes associated with tolerance.1,2 Each of these “mini-withdrawals” reflects transient plasticity in the brain affecting the balance of excitation and inhibition. The simplest description of the changes could be, for example, the ratio of glutamate and gamma-aminobutyric acid (GABA) neurotransmitter activities.
Regulation of GABAA Receptor Gene Expression and Epilepsy
Authors: Brooks-Kayal Amy R. , Russek Shelley J. 
Published: May 2013

Abstract
Results of research in animal models as well as from human retrospective studies suggest that an initial precipitating event such as status epilepticus (SE), stroke, or traumatic brain injury can increase the risk of later development of the recurrent spontaneous seizures that define epilepsy. The process by which a normal brain transforms into one capable of producing recurrent spontaneous seizures, known as epileptogenesis, is likely to be complex and multifactorial. Among the many changes that occur during epileptogenesis are alterations in expression of a wide variety of genes. Determining what molecular pathways regulate these changes in gene expression, and which of them are consequential or causative of disease, are two of the major challenges of research in this area, and are critical to effectively utilizing this information to develop new therapies for the prevention and treatment of epilepsy.
The Voltage-Gated Calcium Channel and Absence Epilepsy
Authors: Noebels Jeffrey L. 
Published: May 2013

Abstract
Voltage-gated calcium channels were the first of now many genetic starting points for tracing the molecular mechanisms of spike-wave seizures, and in so doing, we have gained equally valuable information regarding the neurobiology of the P/Q-type calcium channel and its family members. Perhaps the most important lesson is that the solution of the neurological phenotype requires two steps: first, analyzing how the mutation affects the biology of the channel in a single neuron; second, determining how and when the misbehavior converts normal rebound bursting patterns in the thalamocortical network into an unstable pathological substrate for epilepsy in the developing brain. The “temporary failure of motor and mental functions” defined by Jackson arises not from enhanced excitatory release, as might be expected in paroxysmal hypersynchronous activity, but from the opposite: reduced synaptic strength within the thalamocortical network due to impaired calcium entry and diminished interactions with transmitter release machinery. This reduction in synaptic strength joins other molecular triggers, such as loss of vesicular exocytosis proteins or postsynaptic AMPA receptors, to induce downstream elevations in low voltage-activated T-type calcium channels, which may suffice to generate a spike-wave seizure phenotype. There is ample clinical and genetic evidence to suggest that there will be no uniform thalamocortical molecular pathology underlying this disorder and that alternative routes to the clinical spectrum of absence epilepsy remain to be discovered. Comparisons of their monogenic mechanisms will prove highly instructive in subsequent attempts to unravel the most elusive causes of sporadic generalized epilepsies, those that arise out of polygenic combinations. This category comprises the majority of individuals with absence seizures, and to them we remain obliged to confess our continuing ignorance of the causes of their condition.
Targeting SV2A for Discovery of Antiepileptic Drugs
Authors: Kaminski Rafal M. , Gillard Michel , Klitgaard Henrik 
Published: May 2013

Abstract
Synaptic vesicle 2A constitutes the unique binding site for LEV and plays an important role in synaptic vesicle function. Affinity–potency correlations in several models of partial and generalized epilepsy indicate that SV2A is a broad-spectrum anticonvulsant target. The anticonvulsant activity of LEV is closely linked with occupancy and availability of SV2A, whereas SV2A deficiency leads to increased seizure vulnerability and accelerated epileptogenesis. Taken together, existing experimental data prove that SV2A plays a crucial role in mediating the anticonvulsant action of LEV in vivo and indicate that the SV2A protein represents an important and well-validated target for the discovery of novel AEDs. Finally, the finding that SV2A protein is a clinically validated target for epilepsy has triggered further discovery programs exploring the therapeutic potential for SV2A ligands with different binding properties.
Mechanisms of Ketogenic Diet Action
Authors: Masino Susan A. , Rho Jong M. 
Published: May 2013

Abstract
The evidence for a KD as a successful epilepsy treatment is clear. Multiple retrospective, multi-center, and randomized prospective studies document consistent and significant clinical benefits. The true efficacy of dietary treatments for epilepsy may be underestimated, as the KD is rarely used as a first-line therapy. Certainly, by the time the KD is initiated to thwart medically refractory epilepsy, in some instances the severity of the epileptic condition may be too difficult to overcome. But remarkably, the KD works in the majority of patients who failed to respond to numerous antiepileptic drugs. A detailed understanding of key KD mechanisms could offer a meaningful adjuvant or ultimately the development of a “diet in a pill.”3 But while clinical applications of metabolism-based therapy appear to be growing rapidly, there is a continuing need to develop modified diet formulations with improved efficacy and tolerability (as well as palatability) and to identify new pharmacological targets for drug discovery.
Antiepileptogenesis, Plasticity of AED Targets, Drug Resistance, and Targeting the Immature Brain
Authors: Beck Heinz , Yaari Yoel 
Published: May 2013

Abstract
The cellular basis of epileptic seizures consists of high-frequency, synchronized discharges of neuronal ensembles. The ultimate goal of all antiepileptic therapies is to prevent the occurrence of such episodes or to substantially attenuate their severity. To this end, a multitude of antiepileptic compounds have been developed that are currently in clinical use. However, seizures remain uncontrolled by carefully monitored drug treatment in a substantial portion (∼30%) of epilepsy patients. Therefore, a better understanding of the mode of action of different antiepileptic drugs is mandatory, along with an improved understanding of why these compounds fail in some epilepsy patients, with the ultimate goal of developing new therapeutic avenues. So far, two hypotheses have been advanced to account for the cellular basis of pharmacoresistance in chronic epilepsy. The first hypothesis proposes that pharmacoresistance involves an upregulation of multidrug transporters at the blood-brain barrier. This upregulation limits the access of antiepileptic drugs to the brain parenchyma and therefore leads to a reduced drug concentration at the respective drug target. Because multidrug transporter proteins are of central importance to this hypothesis, it has been termed the transporter hypothesis. The second hypothesis contends that the molecular targets of antiepileptic drugs are modified in chronic epilepsy. Consequently, they are less sensitive to these compounds. This hypothesis has been named the target hypothesis.1,2 Clearly, these two hypotheses are not mutually exclusive. Rather, the underlying mechanisms may coexist and perhaps even act in synergy. The subject of this chapter is the target hypothesis. We describe the molecular mechanisms that alter the targets of antiepileptic drugs and how these mechanisms may interact with altered drug transporter function to cause pharmacoresistance.
Adenosine Augmentation Therapy
Authors: Boison Detlev 
Published: May 2013

Abstract
The ribonucleoside adenosine is based on the purine base adenine, which was most likely already present on the prebiotic primitive Earth.1 Being the core molecule of the energy metabolite adenosine-5′-triphosphate (ATP) as well as being an integral component of both DNA and RNA, adenosine likely played an important role in early evolution as an ideally positioned negative feedback regulator to adjust cellular activity (DNA, RNA) to available energy supplies (ATP). Adenosine has therefore evolved as an important modulator of function in brain, but also in heart, skeletal muscle, kidney, and adipose tissue, in the sense of a “retaliatory metabolite” that protects the cell against excessive external stimulation.2
Late-Onset Mood Disorders
Authors: Peele Roger 
Published: May 2013

Abstract
The history of the International Classification of Diseases [ICD] and the history of the Diagnostic and Statistical Manual [DSM] is reviewed including the present status of both as to the recognition of Late-Onset Depression. Opportunities and challenges to increasing the recognition of Late-Onset Depression in DSMs and ICDs are described, targeting DSM-5, ICD-10-CM or ICD-11.
Comorbid Neurological Illness
Authors: Wint Dylan , Cummings Jeffrey 
Published: May 2013

Abstract
Cerebrovascular disease, movement disorders, epilepsy, and other neurological diseases disproportionately affect the elderly. Prevalence rates of mood disorders, particularly depression, exceed 20% in most neurological disorders. Thus, many mood disturbances in the elderly are comorbid with neurological illness. Furthermore, elderly individuals and neurological patients have high rates of mood-related morbidity and mortality. Unfortunately, mood disorders in neurological conditions are poorly recognized and under-treated. This chapter discusses the problem of mood disorders in specific neurological conditions in the elderly, and provides a general framework for approaching and treating these problems.
Use of Adjunctive Therapy in Older Depressed Adults Who are Resistant to Antidepressant Treatment
Authors: Nelson J. Craig 
Published: May 2013

Abstract
While antidepressants are effective in late life depression, similar to younger patients, a minority of older adults achieve remission with initial treatment. In the 10 placebo controlled trials of second generation antidepressants in older adults, the remission rate was 32.6%. As a consequence adjunctive treatments (addition of a drug not approved for use in depression) or combination treatments (use of two approved antidepressants) are frequently employed, especially in partial responders or to target specific residual symptoms. This chapter reviews the evidence for the efficacy of adjunctive and combination treatments in late life depression. Limited evidence suggests that with 3 to 4 sequential trials, a substantial percentage of older depressed adults will achieve remission.
Novel Platforms for Care Delivery
Authors: Pim Cuijpers Heleen Riper , Beekman Aartjan 
Published: May 2013

AbstractInternet-guided and Telepsychiatry interventions may save costs and time from patients and therapists, they may reach depressed older adults who are not reached with traditional therapies, solve transportation problems, stimulate empowerment of patients, and reduce the stigma associated with mental illness. Although a growing number of studies has examined the effects of Internet-based interventions and telephone-supported interventions, few have examined these in older adults. However, research shows that these interventions are promising and there is no reason to assume that they are not effective in older adults. More research is needed, especially since technological developments are going fast and innovative types of interventions and new possibilities to reduce the disease burden in depressed older adults are emerging rapidly.