Diagnostic criteria for 14 psychiatric illnesses (and for secondary depression) along with the validating evidence for these diagnostic categories comes from workers outside our group as well as from those within; it consists of studies of both outpatients and inpatients, of family studies, and of follow-up studies. These criteria are the most efficient currently available; however, it is expected that the criteria be tested and not be considered a final, closed system. It is expected that the criteria will change as various illnesses are studied by different groups. Such criteria provide a framework for comparison of data gathered in different centers, and serve to promote communication between investigators.

https://jamanetwork.com/HttpHandlers/ArticlePdfHandler.ashx?journal=PSYCH&articleId=490573&pdfFileName=archpsyc_26_1_011.pdf

Diagnostic criteria for use in psychiatric research.

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

The essential amino acid tryptophan is not only a precursor of serotonin but is also degraded to several other neuroactive compounds, including kynurenic acid, 3-hydroxykynurenine and quinolinic acid. The synthesis of these metabolites is regulated by an enzymatic cascade, known as the kynurenine pathway, that is tightly controlled by the immune system. Dysregulation of this pathway, resulting in hyper-or hypofunction of active metabolites, is associated with neurodegenerative and other neurological disorders, as well as with psychiatric diseases such as depression and schizophrenia. With recently developed pharmacological agents, it is now possible to restore metabolic equilibrium and envisage novel therapeutic interventions.

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Kynurenines in the mammalian brain: when physiology meets pathology

Thousands of studies have been conducted of the functioning of the many neurotransmitter systems in order to explore the biologic basis of major depressive disorder. Instead of reviewing this literature exhaustively, we have attempted to propose a model that accommodates the clinical observation that chronic stress early in life in vulnerable persons predisposes them to major depression with contemporary observations of the potential consequences of repeated central nervous system exposure to effectors of the stress response. This model accords with current clinical judgment that major depression is best treated with a combination of psychopharmacologic agents and psychotherapy. Accordingly, whereas psychopharmacologic intervention may be required to resolve an active episode of major depression and to prevent recurrences, psychotherapy may be equally important to lessen the burden of stress imposed by intense inner conflict and counterproductive defenses.

Clinical and biochemical manifestations of depression. Relation to the neurobiology of stress (2)

AN extensive literature exists regarding the relationship of life events and depression. The largest group of studies has concerned the descriptive characterization of those events occurring at the onset of depression. There has been particular emphasis on actual or symbolic losses, 1-4 including loss of self-esteem. 5 Others have been concerned with the general presence or absence of stress at onset and have attempted to define a group of endogenous depressions, occurring in the absence of stress, and showing characteristic clinical features. 6-8 Although it has been generally assumed that most depressions are reactions to events, some dissent has been expressed. Hudgens 9 and his colleagues found events uncommon in the six months prior to onset of illness in 40 patients hospitalized with affective disorders. Winokur and Pitts 10 reported reactive depressions to be infrequent and threw doubt on the validity of

Life Events and Depression: A Controlled Study

Intracellular lithium concentration and clinical response: Towards a membrane theory of depression ☆

Controversies surrounding the distinctions between endogenous and reactive types have characterized the literature on depression. Reviewing seven pertinent factor analytic studies, these authors found sufficient consensus to support the independence of the endogenous and reactive factors. It is suggested, however, that these factors may not represent two etiologically distinct types of depression. The endogenous factor may reflect a "classical" depressive syndrome, whereas the reactive factor may reflect a psychiatric disorder in which depression is only one symptom "contaminated" by other nondepressive clinical features.

The Nosology of Depression: The Endogenous-Reactive Concept

The authors examined the incidence of primary affective disorder (PAD) in relatives of 25 patients with anorexia nervosa and of 25 normal control subjects. Among the relatives of patients with anorexia nervosa, 22% (N = 43) had histories of PAD, while only 10% (N = 17) of the relatives of controls had such histories. Among the PAD relatives of anorectic probands, 34 had histories of unipolar depression and 9 of bipolar affective disorder. These findings provide further evidence of a possible relationship between anorexia nervosa and affective illness.

Primary affective disorder in relatives of patients with anorexia nervosa.

The author reviews the studies of lithium as an antidepressant, evaluates the evidence that there might be specific subgroup of patients for whom it is effective, and reports a study he and his associates conducted that found lithium to be effective for 13 of 21 depressed patients. He concludes that there is convincing, although not conclusive, evidence for an antidepressant effect of lithium and that only by identifying the subgroup of patients for whom it is effective can the continuing uncertainty surrounding lithium's role in affective disorder be resolved. He also calls for a reevaluation of the relationship between mania and depression.

Joe Mendels

Papers

Intracellular lithium concentration and clinical response: Towards a membrane theory of depression ☆

The Nosology of Depression: The Endogenous-Reactive Concept

Primary affective disorder in relatives of patients with anorexia nervosa.

Lithium in the treatment of depression.

Desmethylimipramine-induced decrease in β-adrenergic receptor binding in rat cerebral cortex