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

Erratum: DHEA metabolism to the neurosteroid androsterone: a possible mechanism of DHEA's antidepressant action (DOI: 10.1007/s00213-015-3991-1)

Epidemiologic studies have documented that the majority of women do not become depressed during the menopause transition. However, recent longitudinal studies suggest that in some women, the events related to the menopause transition could play a role in the onset of depression. In this article we review evidence suggesting a relationship between the menopause transition and depression. Additionally, we describe several findings that suggest a role of ovarian hormones in the onset of these depressions, including the clustering of episodes of depression during the stage of the menopause transition that is accompanied by estradiol withdrawal, and the therapeutic effects of short-term estradiol in depressed perimenopausal women. Finally, we discuss possible causes of affective disturbances during the menopause transition.

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Reproductive aging, sex steroids, and mood disorders.

The Neuroendocrinology of Menstrual Cycle Mood Disorders

The pattern and time course of antidepressant response to different treatment modalities provide important clinical information and hints about underlying neurobiological mechanisms. Depressed patients who responded to 1 night's sleep deprivation (11 of 33 patients) showed maximal improvement on day 1 and deterioration in mood thereafter. In contrast, slower onset and more sustained effects were observed following carbamazepine (12 of 37) or electroconvulsive therapy (ECT) (8 of 8). Nearly maximal improvement required about 2 weeks for ECT and 3 weeks for carbamazepine. Possible differential or common biological mechanisms with differential times of action are implied by these data, which are of importance to the neuroscientist attempting to uncover neural substrates of antidepressant response and the clinician attempting to find rapid onset, yet sustained antidepressant treatments.

Differential time course of antidepressant effects after sleep deprivation, ECT, and carbamazepine: Clinical and theoretical implications

Objective To assess the impact of antecedent trauma on the risk of antenatal and postpartum depression in a prospective, longitudinal cohort of pregnant women. Method 374 participants (pregnant women aged 20-34 years) were recruited from a hospital-based obstetrics practice serving a predominantly low-income, inner-city population between May 2007 and May 2012. Clinical diagnostic interviews and psychosocial questionnaires were administered at 18 and 32 weeks of gestation and at 6 weeks and 6 months postpartum. Lifetime exposure to and details of traumatic events were recorded. Depression during pregnancy or the postpartum period was diagnosed according to DSM-IV-TR. Results 39% of the sample reported at least 1 traumatic event; trauma history (odds ratio [OR] = 2.16; 95% CI, 1.31-3.54) and, particularly, experiencing childhood sexual abuse (OR = 2.47; 95% CI, 1.27-4.78), someone close experiencing violence (OR = 2.19; 95% CI, 1.11-4.32), and the unexpected death or illness of someone close (OR = 2.15; 95% CI, 1.14-4.05) predicted antenatal but not postpartum depression. A clear dose-response effect of trauma on antenatal depression was observed; women who experienced 3 or more traumas had a 4-fold risk (OR = 4.34; 95% CI, 2.16-8.70) of antenatal depression compared to women with no trauma history. Conclusions Antecedent trauma significantly increases the risk of antenatal depression, but antenatal depression alone does not appear to predict postpartum depression. Routine screening for trauma exposure and depression is warranted during pregnancy to aid in the early detection and treatment of depression. Future studies need to examine mechanisms that may trigger affective episodes in trauma-exposed women, who may be especially vulnerable to depressive episodes during pregnancy.

David R. Rubinow

Papers

Erratum: DHEA metabolism to the neurosteroid androsterone: a possible mechanism of DHEA's antidepressant action (DOI: 10.1007/s00213-015-3991-1)

Reproductive aging, sex steroids, and mood disorders.

The Neuroendocrinology of Menstrual Cycle Mood Disorders

Differential time course of antidepressant effects after sleep deprivation, ECT, and carbamazepine: Clinical and theoretical implications

Antecedent Trauma Exposure and Risk of Depression in the Perinatal Period