The variable results of positive-negative research with schizophrenics underscore the importance of well-characterized, standardized measurement techniques. We report on the development and initial standardization of the Positive and Negative Syndrome Scale (PANSS) for typological and dimensional assessment. Based on two established psychiatric rating systems, the 30-item PANSS was conceived as an operationalized, drug-sensitive instrument that provides balanced representation of positive and negative symptoms and gauges their relationship to one another and to global psychopathology. It thus constitutes four scales measuring positive and negative syndromes, their differential, and general severity of illness. Study of 101 schizophrenics found the four scales to be normally distributed and supported their reliability and stability. Positive and negative scores were inversely correlated once their common association with general psychopathology was extracted, suggesting that they represent mutually exclusive constructs. Review of five studies involving the PANSS provided evidence of its criterion-related validity with antecedent, genealogical, and concurrent measures, its predictive validity, its drug sensitivity, and its utility for both typological and dimensional assessment.

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The Positive and Negative Syndrome Scale (PANSS) for Schizophrenia

Objective. —This article defines stress and related concepts and reviews their historical development. The notion of a stress system as the effector of the stress syndrome is suggested, and its physiologic and pathophysiologic manifestations are described. A new perspective on human disease states associated with dysregulation of the stress system is provided. Data Sources. —Published original articles from human and animal studies and selected reviews. Literature was surveyed utilizing MEDLINE and the Index Medicus . Study Selection. —Original articles from the basic science and human literature consisted entirely of controlled studies based on verified methodologies and, with the exception of the most recent studies, replicated by more than one laboratory. Many of the basic science and clinical studies had been conducted in our own laboratories and clinical research units. Reviews cited were written by acknowledged leaders in the fields of neurobiology, endocrinology, and behavior. Data Extraction. —Independent extraction and cross-referencing by the authors. Data Synthesis. —Stress and related concepts can be traced as far back as written science and medicine. The stress system coordinates the generalized stress response, which takes place when a stressor of any kind exceeds a threshold. The main components of the stress system are the corticotropin-releasing hormone and locus ceruleus-norepinephrine/autonomic systems and their peripheral effectors, the pituitary-adrenal axis, and the limbs of the autonomic system. Activation of the stress system leads to behavioral and peripheral changes that improve the ability of the organism to adjust homeostasis and increase its chances for survival. There has been an exponential increase in knowledge regarding the interactions among the components of the stress system and between the stress system and other brain elements involved in the regulation of emotion, cognitive function, and behavior, as well as with the axes responsible for reproduction, growth, and immunity. This new knowledge has allowed association of stress system dysfunction, characterized by sustained hyperactivity and/or hypoactivity, to various pathophysiologic states that cut across the traditional boundaries of medical disciplines. These include a range of psychiatric, endocrine, and inflammatory disorders and/or susceptibility to such disorders. Conclusions. —We hope that knowledge from apparently disparate fields of science and medicine integrated into a working theoretical framework will allow generation and testing of new hypotheses on the pathophysiology and diagnosis of, and therapy for, a variety of human illnesses reflecting systematic alterations in the principal effectors of the generalized stress response. We predict that pharmacologic agents capable of altering the central apparatus that governs the stress response will be useful in the treatment of many of these illnesses. ( JAMA . 1992;267:1244-1252)

The Concepts of Stress and Stress System Disorders: Overview of Physical and Behavioral Homeostasis

Memory for a recent event can be expressed explicitly, as conscious recollection, or implicitly, as a facilitation of test performance without conscious recollection. A growing number of recent studies have been concerned with implicit memory and its relation to explicit memory. This article presents an historical survey of observations concerning implicit memory, reviews the findings of contemporary experimental research, and delineates the strengths and weaknesses of alternative theoretical accounts of implicit memory. It is argued that dissociations between implicit and explicit memory have been documented across numerous tasks and subject populations, represent an important challenge for research and theory, and should be viewed in the context of other dissociations between implicit and explicit expressions of knowledge that have been documented in recent cognitive and neuropsychological research. Psychological studies of memory have traditionally relied on tests such as free recall, cued recall, and recognition. A prominent feature of these tests is that they make explicit reference to, and require conscious recollection of, a specific learning episode. During the past several years, however, increasing attention has been paid to experimental situations in which information that was encoded during a particular episode is subsequently expressed without conscious or deliberate recollection. Instead of being asked to try to remember recently presented information, subjects are simply required to perform a task, such as completing a graphemic fragment of a word, indicating

https://scholar.harvard.edu/files/schacterlab/files/schacterimplicitmem1987.pdf

Implicit memory: History and current status.

The neurohypophysial peptide oxytocin (OT) and OT-like hormones facilitate reproduction in all vertebrates at several levels. The major site of OT gene expression is the magnocellular neurons of the hypothalamic paraventricular and supraoptic nuclei. In response to a variety of stimuli such as suckling, parturition, or certain kinds of stress, the processed OT peptide is released from the posterior pituitary into the systemic circulation. Such stimuli also lead to an intranuclear release of OT. Moreover, oxytocinergic neurons display widespread projections throughout the central nervous system. However, OT is also synthesized in peripheral tissues, e.g., uterus, placenta, amnion, corpus luteum, testis, and heart. The OT receptor is a typical class I G protein-coupled receptor that is primarily coupled via Gq proteins to phospholipase C-β. The high-affinity receptor state requires both Mg2+ and cholesterol, which probably function as allosteric modulators. The agonist-binding region of the receptor has bee...

The Oxytocin Receptor System: Structure, Function, and Regulation

Objectives: The purposes of this study were to identify age-related changes in objectively recorded sleep patterns across the human life span in healthy individuals and to clarify whether sleep latency and percentages of stage 1, stage 2, and rapid eye movement (REM) sleep significantly change with age. Design: Review of literature of articles published between 1960 and 2003 in peer-reviewed journals and meta-analysis. Participants: 65 studies representing 3,577 subjects aged 5 years to 102 years. Measurement: The research reports included in this meta-analysis met the following criteria: (1) included nonclinical participants aged 5 years or older; (2) included measures of sleep characteristics by “all night” polysomnography or actigraphy on sleep latency, sleep efficiency, total sleep time, stage 1 sleep, stage 2 sleep, slow-wave sleep, REM sleep, REM latency, or minutes awake after sleep onset; (3) included numeric presentation of the data; and (4) were published between 1960 and 2003 in peer-reviewed journals. Results: In children and adolescents, total sleep time decreased with age only in studies performed on school days. Percentage of slow-wave sleep was significantly negatively correlated with age. Percentages of stage 2 and REM sleep significantly changed with age. In adults, total sleep time, sleep efficiency, percentage of slow-wave sleep, percentage of REM sleep, and REM latency all significantly decreased with age, while sleep latency, percentage of stage 1 sleep, percentage of stage 2 sleep, and wake after sleep onset significantly increased with age. However, only sleep efficiency continued to significantly decrease after 60 years of age. The magnitudes of the effect sizes noted changed depending on whether or not studied participants were screened for mental disorders, organic diseases, use of drug or alcohol, obstructive sleep apnea syndrome, or other sleep disorders. Conclusions: In adults, it appeared that sleep latency, percentages of stage 1 and stage 2 significantly increased with age while percentage of REM sleep decreased. However, effect sizes for the different sleep parameters were greatly modified by the quality of subject screening, diminishing or even masking age associations with different sleep parameters. The number of studies that examined the evolution of sleep parameters with age are scant among school-aged children, adolescents, and middle-aged adults. There are also very few studies that examined the effect of race on polysomnographic sleep parameters.

https://sites.oxy.edu/clint/physio/article/MetaAnalysisofQuantitativeSleepParametersFromChildhoodtoOldAgeOhayon2004.pdf

Meta-Analysis of Quantitative Sleep Parameters From Childhood to Old Age in Healthy Individuals: Developing Normative Sleep Values Across the Human Lifespan

An index of the functional condition of rat sciatic nerve based on measurements made from walking tracks

In order to determine if brain tissue grafts can provide functional input to recipient central nervous system tissue, fetal rat dopamine-containg neurons were implanted adjacent to the caudate nucleus of adult recipients whose endogenous dopaminergic input had been destroyed. The grafts showed good survival and axonal outgrowth. Motor abnormalities, which had been induced by the destruction of the endogenous dopaminergic input to the caudate, were significantly reduced after grafting of the fetal brain tissue. These data suggest that such implants may be potentially useful in reversing deficits after circumscribed destruction of brain tissue.

https://science.sciencemag.org/content/sci/204/4393/643.full.pdf

Brain grafts reduce motor abnormalities produced by destruction of nigrostriatal dopamine system

Context Some, but not all, previous studies suggest that prenatal influenza exposure increases the risk of schizophrenia. These studies used dates of influenza epidemics and maternal recall of infection to define influenza exposure, suggesting that discrepant findings may have resulted from exposure misclassification. Objective To examine whether serologically documented prenatal exposure to influenza increases the risk of schizophrenia. Design Nested case-control study of a large birth cohort, born from 1959 through 1966, and followed up for psychiatric disorders 30 to 38 years later. Setting Population-based birth cohort. Participants Cases were 64 birth cohort members diagnosed as having schizophrenia spectrum disorders (mostly schizophrenia and schizoaffective disorder). Controls were 125 members of the birth cohort, had not been diagnosed as having a schizophrenia spectrum or major affective disorder, and were matched to cases on date of birth, sex, length of time in the cohort, and availability of maternal serum. Main Outcome Measures Archived maternal serum was assayed for influenza antibody in pregnancies giving rise to offspring with schizophrenia and matched control offspring. Results The risk of schizophrenia was increased 7-fold for influenza exposure during the first trimester. There was no increased risk of schizophrenia with influenza during the second or third trimester. With the use of a broader gestational period of influenza exposure—early to midpregnancy—the risk of schizophrenia was increased 3-fold. The findings persisted after adjustment for potential confounders. Conclusions These findings represent the first serologic evidence that prenatal influenza plays a role in schizophrenia. If confirmed, the results may have implications for the prevention of schizophrenia and for unraveling pathogenic mechanisms of the disorder.

https://jamanetwork.com/journals/jamapsychiatry/articlepdf/482040/YOA30021.pdf

Serologic evidence of prenatal influenza in the etiology of schizophrenia

To determine if neuroleptic treatment changes the natural course of schizophrenia, 22 studies were reviewed in which relatively similar patients were or were not given neuroleptics at specific times during the course of their illness. Nineteen of the studies were from first- or predominantly first-break populations. While there was little consensus among the authors of the studies reviewed, a reanalysis of the data indicates that early intervention with neuroleptics in first-break schizophrenic patients increases the likelihood of an improved long-term course. This finding is similar to that of earlier investigators who indicated there was a decrease in patients with the more severe forms of the illness following the introduction of convulsive therapies. Furthermore, there is evidence that stable schizophrenic patients whose neuroleptics are discontinued and have relapses may have a difficult time returning to their previous level of function. The findings describe in this paper have implications for both the treatment of schizophrenia and for understanding the pathophysiological processes that determine the course of the disorder.

https://psycnet.apa.org/journals/szb/17/2/325.pdf

Richard Jed Wyatt

Papers

An index of the functional condition of rat sciatic nerve based on measurements made from walking tracks

Brain grafts reduce motor abnormalities produced by destruction of nigrostriatal dopamine system

Serologic evidence of prenatal influenza in the etiology of schizophrenia

Neuroleptics and the Natural Course of Schizophrenia

Schizophrenia, just the facts: What do we know, how well do we know it?