Seminars in clinical neuropsychiatry最新文献

Each year in the United States approximately 2.5 million Americans incur injuries so severe that they require inpatient admissions to acute care medical settings. This article reviews the development of posttraumatic stress disorder (PTSD) and related comorbid medical conditions among injured trauma survivors. Between 10% and 40% of injured trauma survivors appear to develop PTSD in the weeks and months after their injury. The symptoms of PTSD are clearly linked to a broad spectrum of functional impairment and diminished well-being in injured patients. Although PTSD, depression, somatic amplification, and recurrent substance use are common disturbances after injury, it appears that few symptomatic trauma survivors receive formal mental health evaluation or treatment. Substantial perceived and structural barriers to accessing care exist for injured trauma survivors. The public health significance of these findings is discussed and implications for future intervention development are explored in the following chapters.

Nearly half of injured trauma survivors suffer from substance use disorders, particularly alcohol and stimulants. Substance abuse screenings and brief interventions are essential components of collaborative care for trauma patients. If provided by trauma centers, brief interventions can reduce drinking and injury recidivism for up to 1 year after hospital discharge. First, this report explains the rationale for such a service as well as the theoretical underpinnings of brief behavior change interventions. Next, a literature review is presented regarding the outcomes of brief interventions for substance abuse, both in general medical settings and in trauma centers. Finally, a description is provided of a level 1 trauma center's screening and brief intervention service that uses motivational interviewing, has developed over a decade, and has been evaluated in a randomized trial. The inpatient and outpatient intervention protocols for this service are detailed, as well as the specific clinical challenges encountered.

The secondary prevention of posttraumatic stress disorder (PTSD) and related comorbidities among injured trauma survivors constitutes an important public health problem. This article outlines quality-of-care criteria that are intended to guide intervention development for PTSD in the acute care medical setting. The multiple demographic, injury, and service delivery system factors that characterize the acute care setting's clinical heterogeneity are discussed. A model of intervention development that begins with population-based descriptive studies and small pilots of efficacious PTSD treatments and evolves to the development of larger-scale multifaceted collaborative interventions is introduced. Collaborative interventions hold promise for injured trauma survivors treated in acute care settings because they combine evidence-based PTSD interventions and patient-centered supportive care.

This article discusses the applicability of cognitive-behavioral therapy (CBT) to the treatment of injured trauma survivors, with special consideration of treatment delivery within the trauma care system. The theoretical underpinnings and major treatment components of CBT for posttraumatic stress disorder (PTSD) are presented, followed by a review of the treatment outcome research to date. As few studies have evaluated CBT for injured trauma survivors, specifically, circumstances and comorbidities of this population, that might impact treatment delivery and outcome are discussed within a cognitive-behavioral framework. The article concludes with recommendations for research and treatment of PTSD among injured trauma survivors that draw from cognitive-behavioral theory and empirically supported principles of change.

Brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family of survival-promoting molecules, plays an important role in the growth, development, maintenance, and function of several neuronal systems. The purpose of this article is to point out evidence for the involvement of this molecule in the maintenance of normal cognitive and emotional functioning, and to outline recent developments using BDNF, or the regulation of endogenous BDNF expression, in the treatment of a variety of mental disorders. This article discusses the important role of BDNF in neuronal growth and survival, in modulating neurotransmission, in activity-directed synaptic remodeling, and in adult neurogenesis. We next outline evidence for the involvement of BDNF in complex behaviors such as learning, feeding, locomotion, responses to painful stimuli, and the management of severe stress. Finally, our review focuses on the involvement of BDNF in treatments for clinical depression and other chronic neurodegenerative processes. We discuss the way that current and future treatment development can be guided by our growing understanding of this molecule's actions in the brain and the ways the expression of BDNF can be regulated.

The endogenous neuropeptide, 5-HT-moduline, selectively and allosterically interacts with 5-HT(1B) receptors. By binding at a site distinct from that bound by 5-HT, 5-HT-moduline induces structural changes in 5-HT(1B) receptors or stabilizes a particular conformation of these receptors. These conformational changes ultimately lead to the prevention of 5-HT binding resulting in desensitization of these receptors and reduction of the serotonergic function. The efficacy of 5-HT(1B) receptor agonists, for example, has been shown to be reduced by this peptide in vitro and behaviorally. In addition, 5-HT-moduline increases 5-HT release, which is regulated by presynaptic 5-HT(1B) autoreceptors. The release of 5-HT-moduline itself is increased after acute restraint stress in rats, whereas deactivation of 5-HT-moduline by specific antibodies in mice prevents the development of anxiety in a classic behavioral model, suggesting a potential role of the peptide in the control of anxiety. It is thus hypothesized that agents inhibiting the effect of 5-HT-moduline could have anxiolytic activity. Because the serotonergic activity is known to play a key role in psychiatric disorders such as depression and anxiety, compounds capable of mimicking or inhibiting the activity of 5-HT-moduline can represent novel antidepressants or anxiolytics.

Corticotropin-releasing factor (CRF) and related neuropeptides such as urocortin are key mediators of stress in the central nervous system. Through two types of G-protein-linked receptors, they play important roles in stress and its relationship to a variety of psychiatric illnesses. CRF appears to play an important role in regulating key neural systems involved in controlling mood, anxiety, feeding behavior, and the interactions between stress and drug addiction. Our improved understanding of the actions of CRF and related peptides reveals not only mechanisms by which stress affects behavior, but also new opportunities to intervene in psychiatric disorders related to stress exposure.

Over the past three decades, the hormone insulin has been acknowledged to have multiple effects in the brain, and its role has been validated by the identification of receptors and a transport system for insulin in the central nervous system. Much research has focused on the action of insulin to participate in a feedback loop for the regulation of energy balance. Additionally, more recent studies are demonstrating effects of insulin on brain reward pathways; insulin can interact directly with limbic circuitry to decrease the rewarding or reinforcing value of experimental and natural stimuli, including food. These studies are reviewed in the context of current knowledge of insulin action in the brain, and we offer speculation regarding the relevance of this expanded role of insulin in mental disorders.

Schizophrenia is one of the major psychiatric disorders for which effective pharmacotherapy has been available for approximately 50 years. Study of the mechanism of action of these antipsychotic drugs (APDs) has largely focused on the mesolimbic dopamine system and in the neurotransmitter systems that regulate it. Modulation of the neurotensin (NT) circuit in the mesolimbic system can underlie the mechanism of action of APDs. Several lines of evidence support this hypothesis, including: (1) association of NT with neural circuits relevant to the pathophysiology of schizophrenia and the therapeutic effects of APDs; (2) prediction of antipsychotic efficacy and side effect liability based on APD effects on the NT system; (3) low concentrations of NT in the cerebrospinal fluid of a subset of patients with schizophrenia and its normalization after associated clinical improvement with APDs; and (4) remarkable behavioral similarities between peripherally administered APDs and central NT administration. For these reasons, drugs that directly modify the activity of NT systems, particularly NT receptor agonists, could plausibly represent a novel class of APDs.

Mild cognitive impairment (MCI) is a prevalent condition among older adults that carries a high risk of progression to Alzheimer's disease or other dementias. Given the potential for delaying or preventing the onset of dementia, efforts aimed at early detection and early intervention are important. The current paper reviews the conceptualization and diagnosis of MCI, assessment of memory complaints and deficits in the elderly, as well as recent research on the neurobiological basis of the disorder, including neurochemical, structural, and functional neuroimaging findings.