搜索结果：Schizophrenia bulletin

In the "Special Report on Schizophrenia" published in the Schizophrenia Bulletin in 1987, the genetic basis of schizophrenia was reviewed. Here, we provide our perspective on the current status of this area of investigation, focusing largely but not exclusively on recent findings. Methodologically rigorous family studies have now clearly shown that schizophrenia substantially aggregates in families. Familial factors that predispose to schizophrenia also increase the risk for certain schizophrenia-related personality disorders and probably for some forms of non-schizophrenic nonaffective psychosis. Results from one new twin study and updates from two ongoing adoption studies continue to support the hypothesis that genetic factors play a major role in the etiology of schizophrenia. Little is known about how genetic liability to schizophrenia is transmitted, although statistical models suggest that transmission is probably not due solely to a single major gene. Schizophrenia is clearly a complex disorder in that gene carriers need not manifest the illness (incomplete penetrance), affected individuals need not have the gene (environmental forms of phenocopies), diagnostic uncertainties cannot be avoided, and different families may carry different susceptibility genes (genetic heterogeneity). Therefore, segregation or linkage analyses are far more difficult to perform with schizophrenia than with Mendelian genetic disorders. Given this complexity, it is not too surprising that no replicated positive evidence for linkage to schizophrenia has been reported to date. However, just as linkage analysis of schizophrenia should not be excessively embraced as the only form of viable genetic research in schizophrenia, it also shouldn't be prematurely spurned. If one or several genes of major effect exist for schizophrenia, large samples using new statistical and laboratory methodologies have a good chance of detecting them. The authors thus recommend a balanced research approach to the genetics of schizophrenia that includes traditional methods of family, twin, and adoption studies as well as a major effort in large-sample linkage studies.

Although a decade has passed since the genetics of schizophrenia was examined for the Schizophrenia Bulletin, the epigenetic puzzle of schizophrenia has not yielded its secrets to any scientific break-through. In this article we review a sample of the highlights relevant to enlightened genetic thinking, i.e., a broad diathesis-stressor framework with multifactorial causation assumed and with provision for the epigenetic interaction of psychosocial as well as neurobiological factors. The clinical genetic epidemiologist needs to know the lifetime morbid risks generated by different definitions of schizophrenia, as well as the consequences for the familial risks generated by the various family, twin, and adoption strategies. Schizophrenia appears to occur through an interaction of a genetic susceptibility with some kind of environmental stress; the stress need not be an environment containing a person with a diagnosis in the schizophrenia spectrum; the genetic factors in schizophrenia have specificity as they do not increase the risk for major affective disorders or delusional disorder. Clearly, schizophrenia is clinically or phenotypically heterogeneous, but whether this variety is paralleled by etiological heterogeneity or to what extent is problematic. Once the existence of an important genetic predisposition to developing schizophrenia has been established, it becomes important to provide a theory (or theories) to account for its mode (modes) of transmission. Psychiatric geneticists have not yet solved the problem, in part because of the difficulty of specifying the appropriate phenotype to analyze and also because of the unknown degree of heterogeneity. Genetic markers are a special category of biological markers. In addition to conventional markers, the advent of "the new genetics" of recombinant DNA has meant that many more genetic markers (probes) are now available and that the day is not far off when the human genome will be extensively mapped. Considerable optimism exists about the future usefulness of genetic markers in detecting major gene effects and resolving problems of heterogeneity in schizophrenia.

The genetics of schizophrenia has been approached utilizing a variety of methods. One emerging strategy is the use of endophenotypes in order to understand and identify the functional importance of genetically transmitted, brain-based deficits across schizophrenia kindreds. The endophenotype strategy is a topic of this issue of Schizophrenia Bulletin. Endophenotypes are quantitative, heritable, trait-related deficits typically assessed by laboratory-based methods rather than clinical observation. Endophenotypes are seen as closer to genetic variation than are clinical symptoms of schizophrenia, and are therefore closely linked to heritable risk factors. There has been a broad expansion of opportunities available to psychiatric neuroscientists who use the endophenotype strategy to understand the genetic basis of schizophrenia. In this context, genetic variation such as single nucleotide polymorphisms (SNPs) induces abnormalities in endophenotypic domains such as neurocognition, neurodevelopment, metabolism, and neurophysiology. This article discusses the challenges that abound in genetic research of schizophrenia, including issues in ascertainment, epistasis, ethnic diversity, and the potentially normalizing effects of second-generation antipsychotic medications on neurocognitive and neurophysiological measures. Robust strategies for meeting these challenges are discussed in this review and the subsequent articles in this issue. This article summarizes conceptual advances and progress in the measurement and use of endophenotypes in schizophrenia that form the basis of the multisite National Institute of Mental Health Consortium on the Genetics of Schizophrenia. The endophenotype strategy offers powerful and exciting opportunities to understand the genetically conferred neurobiological vulnerabilities and possible new strong inference and molecularly based treatments for schizophrenia.

Approximately 1% of the population is diagnosed with schizophrenia, and despite longstanding critiques of the (bio)medical model, understanding of the disorder still arises primarily through (bio)medical explanations. In turn, causation, symptoms and treatments are increasingly sophisticated and well known while understanding of other aspects of the disorder, especially the intersubjective experience of people living with schizophrenia, remains fragmented. For this reason, the present study sought to understand how people experience schizophrenia. To do this, the stories of 19 people diagnosed with the disorder were hermeneutically interpreted. These stories appeared in The Schizophrenia Bulletin--a journal which publishes 'first person accounts', sometimes anonymously, of people's experience of mental illness. Within the study context, the findings indicate that facing the adversity of schizophrenia means living: (i) wisely--understanding the nature of self-with-schizophrenia and of life-with-schizophrenia; (ii) mindfully--keeping understandings in conscious thought; and (iii) purposefully--acting deliberately. Doing this results in a stable and meaningful life and in a different, more resilient self.

The last 10 years of schizophrenia research have indicated a renewed interest in understanding gender differences in schizophrenia. The purpose of this special edition of the Schizophrenia Bulletin is to bring together recent research on gender and schizophrenia across a variety of substantive domains of interest in the study of schizophrenia. Gender differences in schizophrenia have been found in the areas of premorbid history, symptomatology, brain morphology, brain functioning, neurochemistry, family transmission, course, and treatment response. The findings are not necessarily consistent across studies, and the diagnostic specificity of the gender effects must still be addressed. This article introduces the studies presented in this issue, attempts to address some of the inconsistencies, and provides a brief synthesis of findings and directions for future research.

The concept of schizotypy represents a rich and complex psychopathology construct. Furthermore, the construct implies a theoretical model that has considerable utility as an organizing framework for the study of schizophrenia, schizophrenia-related psychopathology (eg, delusional disorder, psychosis-NOS (not otherwise specified), schizotypal, and paranoid personality disorder), and putative schizophrenia endophenotypes as suggested by Rado, Meehl, Gottesman, Lenzenweger, and others. The understanding (and misunderstanding) of the schizophrenia-related schizotypy model, particularly as regards clinical illness, as well as an alternative approach to the construct require vigilance in order to ensure the methodological approach continues to yield the fruit that it can in illuminating the pathogenesis of schizophrenia-related psychopathology. The articles in the Special Section in this issue of Schizophrenia Bulletin highlight methodological and theoretical issues that should be examined carefully.

Descriptions of various psychotic symptoms in children began to appear in the psychiatric literature at about the same time as descriptions of psychotic symptoms in adults. For example, Kraepelin estimated that at least 3.5 percent of his cases of dementia praecox had onsets before age 10. The construct of "childhood schizophrenia" initially emerged from attempts to classify a broad range of psychotic children. By the late 1940s and 1950s, the diagnosis of "childhood schizophrenia" was given to many disturbed children who today would be considered to have infantile autism and other developmental disabilities. In the early 1970s infantile autism and its variants was differentiated from schizophrenia of childhood onset. These changes were incorporated in DSM-III, which returned to the practice before 1930 of diagnosing schizophrenia in children using the same criteria as for adults, with minor allowances for differences in the manifestations of these symptoms during childhood. The studies presented in this issue of Schizophrenia Bulletin use DSM-III, DSM-III-R, or ICD-9 criteria for schizophrenia.

Beginning in 1992, the Agency for Health Care Policy and Research and the National Institute of Mental Health funded the Schizophrenia Patient Outcomes Research Team (PORT) to develop and disseminate recommendations for the treatment of schizophrenia based on existing scientific evidence. These Treatment Recommendations, presented here in final form for the first time, are based on exhaustive reviews of the treatment outcomes literature (previously published in Schizophrenia Bulletin, Vol. 21, No. 4, 1995) and focus on those treatments for which there is substantial evidence of efficacy. The recommendations address antipsychotic agents, adjunctive pharmacotherapies, electroconvulsive therapy, psychological interventions, family interventions, vocational rehabilitation, and assertive community treatment/intensive case management. Support for each recommendation is referenced to the previous PORT literature reviews, and the recommendations are rated according to the level of supporting evidence. The PORT Treatment Recommendations provide a basis for moving toward "evidence-based" practice for schizophrenia and identify both the strengths and limitations in our current knowledge base.

A replication is reported of a three-factor--active, withdrawn, unreality--structure of schizotypy measured with the Schizotypal Personality Questionnaire (SPQ) in the normal population, a structure which has close affinities with a three-syndrome model of schizophrenia. Cognitive asymmetry patterns and arousal scales are found in the companion report--Part II in this issue of the Schizophrenia Bulletin. Here the withdrawn factor--loneliness and constricted affect--was also complemented by the physical anhedonia scale. The original sample (1995) was then combined with the replication sample to examine associations with the dimensions of extraversion-introversion, neuroticism, and psychoticism. Introversion loaded on the first withdrawn factor. The second unreality factor--unusual perceptions, magical beliefs, and ideas of reference--was unrelated to the Eysenck dimensions. Psychoticism loaded on the third active factor--eccentricity and odd speech. Neuroticism formed a fourth, nonspecific factor with social anxiety and suspiciousness. Insufficiencies in current measures of the structure of schizotypy and schizophrenia are discussed. These include the absence of activity-arousal from the SPQ, the limited assessment of cognitive disorganization in schizotypy, and its heterogeneity in schizophrenia. The history of the active-withdrawn classification and its importance in further elucidation of schizotypy and schizophrenia are outlined.

Clinical and experimental research have provided anatomical, pharmacological, and behavioral evidence for a prominent prefrontal dysfunction in schizophrenia. Negative symptoms and behavioral disorganization in the disorder can be understood as a failure in the working memory functions of the prefrontal cortex by which information is updated on a momentto-moment basis or retrieved from long-term stores, held in mind, and used to guide behavior by ideas, concepts, and stored knowledge. This article recounts efforts to dissect the cellular and circuit basis of working memory with the goal of extending the insights gained from the study of normal brain organization in animal models to an understanding of the clinical disorder; it includes recent neuropathological findings that indicate that neural dystrophy rather than cell loss predominates in schizophrenia. Evidence from a variety of studies is accumulating to indicate that dopamine has a major role in regulating the excitability of the cortical neurons upon which the working memory function of the prefrontal cortex depends. Interactions between monoamines and a compromised cortical circuitry may hold the key to the salience of frontal lobe symptoms in schizophrenia, in spite of widespread pathological changes. We outline several direct and indirect intercellular mechanisms for modulating working memory function in the prefrontal cortex based on the localization of dopamine receptors on the distal dendrites and spines of glutamatergic pyramidal cells and on gamma-aminobutyric acid (GABA)ergic intemeurons in the prefrontal cortex. Understanding the interactions between the major cellular constituents of cortical circuits-pyramidal and nonpyramidal cells-is a necessary step in unraveling the receptor mechanisms, which could lead to an effective pharmacological treatment of negative and cognitive symptoms, as well as improved insight into the pathophysiological basis of the disorder. Schizophrenia Bulletin, 23(3):437-^*58,1997.

The article summarizes the process used to distill schizophrenia science into 22 facts. These facts consist of 6 basic facts, 3 etiological facts, 6 pharmacological and treatment facts, 5 pathology facts, and 2 behavioral facts that were critically reviewed by the scholarly community through a special initiative in cooperation with the Schizophrenia Research Forum. A subset of 10 of these facts was selected to form a common set of findings to be explained from the different theoretical perspectives included in this special section of Schizophrenia Bulletin. The rationale for this exercise is to distinguish more precisely the areas of agreement and disagreement between theories of schizophrenia and to highlight where more thought and data can make the greatest impact for understanding this disease.

The article that follows is part of the Schizophrenia Bulletin's ongoing First Person Account series. We hope that mental health professionals—the Bulletin's primary audience—will take this opportunity to learn about the issues and difficulties confronted by consumers of mental health care. In addition, we hope that these accounts will give patients and families a better sense of not being alone in confronting the problems that can be anticipated by persons with serious emotional difficulties. We welcome other contributions from patients, ex-patients, or family members. Our major editorial requirement is that such contributions be clearly written and organized, and that a novel or unique aspect of schizophrenia be described, with special emphasis on points that will be important for professionals. Clinicians who see articulate patients with experiences they believe should be shared might encourage these patients to submit their articles to Schizophrenia Bulletin, First Person Accounts, EEl Communications, 66 Canal Center Plaza, Suite 200, Alexandria, VA 22314.—The Editors.

In a recent article, Andreasen and Flaum (Schizophrenia Bulletin, Vol. 17, No. 1, 1991) argued that greater emphasis should be placed on negative symptoms in the diagnosis of schizophrenia, leading to a less important role for positive symptoms. This article presents a counter-argument to this view. Positive symptoms are common and reliable and therefore highly useful diagnostically. First-rank symptoms, although not specific to schizophrenia, show good discriminability. No other type of symptom or investigative method can make such claims to usefulness. Although positive symptoms do not predict outcome, this is not a necessary function of diagnostic criteria. The predictive power of negative symptoms is, in any case, based largely on studies of patients with chronic disorder. Premorbidly impaired social development may interact with schizophrenia, worsening the prognosis. We believe positive symptoms have always been the essence of psychiatric disorder and should remain so. Increasing the diagnostic weight given to negative symptoms risks restricting the definition of schizophrenia excessively.

In light of the large number of studies published since the 2004 update of Schizophrenia Patient Outcomes Research Team psychopharmacological treatment recommendations, we conducted an extensive literature review to determine whether the current psychopharmacological treatment recommendations required revision and whether there was sufficient evidence to warrant new treatment recommendations for prespecified outcomes of interest. We reviewed over 400 articles, which resulted in 16 treatment recommendations: the revision of 11 previous treatment recommendations and 5 new treatment recommendations. Three previous treatment recommendations were eliminated. There were 13 interventions and/or outcomes for which there was insufficient evidence for a treatment recommendation, and a statement was written to summarize the current level of evidence and identify important gaps in our knowledge that need to be addressed. In general, there was considerable consensus among the Psychopharmacology Evidence Review Group and the expert consultants. Two major areas of contention concerned whether there was sufficient evidence to recommend specific dosage ranges for the acute and maintenance treatment of first-episode and multi-episode schizophrenia and to endorse the practice of switching antipsychotics for the treatment of antipsychotic-related weight gain. Finally, there continue to be major gaps in our knowledge, including limited information on (1) the use of adjunctive pharmacological agents for the treatment of persistent positive symptoms or other symptom domains of psychopathology, including anxiety, cognitive impairments, depressive symptoms, and persistent negative symptoms and (2) the treatment of co-occurring substance or medical disorders that occur frequently in individuals with schizophrenia. (Reprinted with permission from Schizophrenia Bulletin 2010; 36:71–93)

This special issue of the Schizophrenia Bulletin focuses on three brain areas hypothesized to play a role in the etiology of schizophrenia--the frontal lobes, the basal ganglia, and the temporal lobes. Contributors to the issue review evidence from brain-imaging, post-mortem, and psychopharmacological studies that support the involvement of each of these important brain areas in schizophrenia. It is concluded that theories emphasizing cortical/subcortical interconnections rather than a single brain area provide the greatest challenge, and also the greatest promise, to schizophrenia researchers.

The first aim of this issue of the Schizophrenia Bulletin is to provide an up-to-date review of the major domains of research in the experimental psychopathology of schizophrenia, in which important contributions to our understanding of putative pathophysiologic mechanisms have been made. This research has identified several biobehavioral traits as measures of enhanced liability to schizophrenia. Rather than present a substantive review of the research on a particular trait, the authors of several articles focus on a critical appraisal and evaluation of the literature since 1987 in their particular area. The second aim of this issue is to present new methodologic approaches and conceptualizations for incorporating biobehavioral trait data in future psychiatric research designs. Now is the time not only to recognize past contributions but also to recognize that further advances in our understanding of the etiology and pathophysiology of schizophrenia may depend on continued research in experimental psychopathology that culminates in an integration in both methods and research design across disparate scientific fields.

Current recommendations for evidence-based schizophrenia treatment support a comprehensive, individualized approach that integrates advances in psychopharmacology with psychosocial strategies for disease management. In this issue of the Schizophrenia Bulletin, we invited clinician investigators to summarize new empirical data concerning the efficacy of psychosocial interventions that target common and particularly problematic aspects of schizophrenia. A rich formulary of psychosocial interventions with demonstrated efficacy is now available. With new neuroleptic medications, these interventions should define the current standard of care for schizophrenia.