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

The secretion of glucocorticoids (GCs) is a classic endocrine response to stress. Despite that, it remains controversial as to what purpose GCs serve at such times. One view, stretching back to the time of Hans Selye, posits that GCs help mediate the ongoing or pending stress response, either via basal levels of GCs permitting other facets of the stress response to emerge efficaciously, and/or by stress levels of GCs actively stimulating the stress response. In contrast, a revisionist viewpoint posits that GCs suppress the stress response, preventing it from being pathologically overactivated. In this review, we consider recent findings regarding GC action and, based on them, generate criteria for determining whether a particular GC action permits, stimulates, or suppresses an ongoing stressresponse or, as an additional category, is preparative for a subsequent stressor. We apply these GC actions to the realms of cardiovascular function, fluid volume and hemorrhage, immunity and inflammation, metabolism, neurobiology, and reproductive physiology. We find that GC actions fall into markedly different categories, depending on the physiological endpoint in question, with evidence for mediating effects in some cases, and suppressive or preparative in others. We then attempt to assimilate these heterogeneous GC actions into a physiological whole. (Endocrine Reviews 21: 55‐ 89, 2000)

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How do glucocorticoids influence stress responses? Integrating permissive, suppressive, stimulatory, and preparative actions.

In response to a peripheral infection, innate immune cells produce pro-inflammatory cytokines that act on the brain to cause sickness behaviour. When activation of the peripheral immune system continues unabated, such as during systemic infections, cancer or autoimmune diseases, the ensuing immune signalling to the brain can lead to an exacerbation of sickness and the development of symptoms of depression in vulnerable individuals. These phenomena might account for the increased prevalence of clinical depression in physically ill people. Inflammation is therefore an important biological event that might increase the risk of major depressive episodes, much like the more traditional psychosocial factors.

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From inflammation to sickness and depression: when the immune system subjugates the brain

The detection of psychiatric illness by questionnaire

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

This paper reports the reduction of the concentration of the neuropeptide somatostatin in the CSF of patients with affective illness during treatment with the anticovulsant carbamazepine. None of the other psychotropic agents used in this study similarly affected CSF somatostatin, although zimelidine appeared to increase CSF somatostatin in a small number of patients. The potential mechanism and significance of the effects of carbamazepine on CSF somatostatin are discussed in relation to the psychotropic, anticonvulsant, and analgesic properties of carbamazepine.

Effects of carbamazepine on cerebrospinal fluid somatostatin

Mood disturbances have been identified in association with changes in levels of reproductive hormones. The use of hormonal measures in the diagnosis of reproductive endocrine-related mood disorders is highly variable, ranging from necessary in perimenopausal depression to irrelevant in premenstrual syndrome. This article describes our view of the use of hormonal measures for diagnostic and research purposes in perimenopausal depression and premenstrual syndrome. We suggest that the understanding of these disorders lies in as yet unidentified contextual factors rather than in hormonal excesses or deficiencies.

Hormone measures in reproductive endocrine-related mood disorders: diagnostic issues.

Steroid modulation of human memory: biochemical correlates.

We have examined the relationship between thyroid function and the presence of symptoms in women with prospectively confirmed premenstrual syndrome (PMS) in the following ways: 1) basal thyroid function tests (n = 124); 2) thyroid auto-antibody levels (n = 63); 3) TRH stimulation tests performed during the follicular phase (n = 39) or during both the follicular and luteal phase (n = 21); and 4) the efficacy of L-T4 in the treatment of PMS (n = 30). Results: Thirteen women (10.5%) had basal evidence of either grade I or II hypothyroidism or hyperthyroidism. Elevated thyroid auto-antibody titers were observed in eight women (13%). Eighteen women (30%) (all with normal basal TSH levels) had abnormal responses to TRH, either blunted (n = 6) or exaggerated (n = 12). L-T4 was not superior to placebo in the treatment of PMS in a double blind placebo controlled cross-over trial. Although it is clear that PMS is not simply masked hypothyroidism, abnormalities of stimulated thyroid function appear with greater than...

Thyroid function in women with premenstrual syndrome.

Background: Previous studies suggest that women with premenstrual syndrome (PMS) differ from those without PMS in measures of personality. The purpose of this study was to measure the effect of menstrual cycle phase on personality variables in women with and without PMS. Method: The Personality Diagnostic Questionnaire-Revised (PDQ-R) was administered in both the follicular and luteal phases to women with PMS (according to National Institute of Mental Health PMS Workshop Diagnostic Guidelines) (N = 40). An asymptomatic control group (N = 20) as well as a symptomatic group of women with DSM-IV-diagnosed recurrent, non-menstrual-cycle-related brief depression (N = 20) also completed the questionnaire in both phases. Results: Only women with PMS demonstrated a significant increase in total PDQ-R score (reflecting overall personality disorder) from the follicular to the luteal phase (p <.01). Women with PMS had significantly higher total PDQ-R scores than the asymptomatic controls during both the follicular (p <.05) and luteal (p <.01) phases, whereas there was no significant difference between women with PMS and symptomatic controls during either phase. Subscale scores fit similar patterns, as did the number of women in each group meeting a cutoff score indicative of the presence of personality dysfunction. Conclusion: In this preliminary study, women with PMS were unique in demonstrating a menstrual cycle phase effect on PDQ-R score, while their scores in both phases were closer to symptomatic controls than asymptomatic controls. These findings suggest that personality disorder in women with PMS may have both state- and trait-related components.

David R. Rubinow

Papers

Effects of carbamazepine on cerebrospinal fluid somatostatin

Hormone measures in reproductive endocrine-related mood disorders: diagnostic issues.

Steroid modulation of human memory: biochemical correlates.

Thyroid function in women with premenstrual syndrome.

Effects of the menstrual cycle on measures of personality in women with premenstrual syndrome: a preliminary study.