Should we expect "neural signatures" for DSM diagnoses?

Contemporary researchers in psychiatry have sought to develop a nosology based on empirical observation, in line with the principles spelled out by Drs Eli Robins and Samuel B. Guze in 1970. For more than 2 decades, psychiatrists using neuroimaging have aspired to provide one form of "laboratory study" that Robins and Guze said would have to be in place for a psychiatric diagnosis to be valid: researchers have sought "neural signatures" of psychiatric disorders. Our objective was to examine the feasibility of this endeavor. To this end, we examine whether current psychiatric nosology as defined in the Diagnostic and Statistical Manual of Mental Disorders (DSM) lends itself to the identification of neural signatures for psychiatric diagnoses. Because neuroimaging largely is used only to detect average activation or structural differences between groups of individuals with the same diagnosis and groups of individuals with no diagnosis, it is unlikely that it will be possible to use neuroimaging technologies to determine which psychiatric diagnosis a given individual warrants. In addition, the heterogeneity of psychiatric disorder categories as defined in the DSM reveals that these diagnoses do not reflect neurologically discrete phenomena. Finally, neural correlates of psychopathology generally are not unique to specific diagnoses. Although it is unrealistic to hope that neuroimaging will be used to make psychiatric diagnoses as they are currently conceived, neuroimaging is already being used to make headway in 2 other arenas of psychiatric investigation that we briefly review.     

Philosophy and the DSM-III.

This report explores the interface between psychiatry and the DSM-III, arguing that philosophy and psychiatry are of value to one another. Three trends within philosophy are delineated--positivism, hermeneutics, and a synthetic position. These trends are applied to the DSM-III and to specific issues in psychiatric nosology such as the definition of mental disorder, the question of establishing boundaries between different psychiatric disorders, and the differentiation of organic and functional disorders. It is argued that while nosologists often think of themselves along positivist lines, and are often criticized by hermeneutic thinkers for just these assumptions, a synthetic view accounts best for how psychiatric science works. It is concluded that philosophy undergirds psychiatric nosology, while psychiatric nosology raises a series of philosophical questions.     

Reflections on the relationship between psychiatric genetics and psychiatric nosology

Research advances in psychiatric genetics have raised expectations that genetic findings might lead to major breakthroughs in psychiatric nosology. The author reviews the plausibility of these claims. Four areas are addressed. First, it is argued that familial aggregation of a single putative psychiatric syndrome provides at best limited evidence for the validity of that syndrome. Second, both traditional and molecular genetic strategies can supply important insights into major diagnostic conundrums. However, evidence that one or a few individual genes impact on risk for two disorders is not likely to resolve definitively the nosologic relationship between the two syndromes. Third, while gene-based essentialist models for psychiatric disorders are conceptually appealing, they are not well supported empirically. Gene discovery in psychiatry is, on its own, unlikely to allow us to "carve nature at its joints," thereby validating categorical psychiatric diagnoses. Fourth, the project to ground "messy" psychiatric categories on the firm foundation of genes-as an archetypal natural kind-may be fundamentally flawed because the very concept of "the gene" as a discrete entity is itself increasingly in doubt. Whereas psychiatric genetics has and will continue to provide important insights into the etiology of psychiatric and substance use disorders, it is not likely alone to provide deep answers to the complex and multifaceted problems facing psychiatric nosology.     

Genetics, neuroscience and psychiatric classification

Some psychiatrists anticipate a revolution in psychiatric nosology, on the basis of emerging data from genetics and genomics. There are, however, good empirical and conceptual reasons to resist any such revolution. Basing an understanding of psychiatric entities on one of multiple biological (not to mention sociocultural and psychological) considerations is a specious method of approaching the project of psychiatric taxonomy. A classification system that lacks sufficient consensus on the phenomenology of those classified cannot be adequately buttressed by exclusively genetic accounts. This paper advocates a more diversely informed nosology that, in turn, fosters attention to broader diagnostic considerations. We explore more plausible ways in which genetics and genomics, in conjunction with neuroscience and other biological disciplines, can help to shape diagnostic classification in psychiatry. There are, of course, differing views on the degree of prominence that genetics should take in psychiatric diagnosis and classification. We outline these accounts in illustration of this continuum. Drawing on Wimsatt's work on robustness analysis, we dismiss optimistic scenarios about the potential nosological advantages of psychiatric genetics and genomics, and offer a novel defense of realism about psychiatric entities. We also briefly sketch an integrative methodology for psychiatric research and classification.     

Psychophysiological predictors of drug treatment response

Few of the psychophysiologic findings reviewed above are diagnostically specific. Not all persons given the same psychiatric diagnosis are likely to share the biological characteristic while others with different diagnoses do. The first and most simple explanation commonly offered is to refer to inadequacies in clinical diagnostic procedures or in the particular diagnostic system that was used in the study. It is true that the reliability of psychiatric ratings are typically lower than the reliability of psychophysiologic measures, but the situation appears to be more complex. In considering the issue of the relationship between psychiatric diagnosis and psychophysiological data, it is important to realize that psychiatric diagnosis may have several purposes only one of which is predicting drug treatment response. In addition, the degree to which a biological characteristic is present before the illness and between episodes, or in relatives or normal subjects having traits suggestive of vulnerability to the disorder, are important aspects of psychophysiological investigations. The state vs trait nature of the measure is of frequent concern, and changes in a psychophysiologic measure as a function of drug treatment are considered a part of this broader issue. Furthermore, psychophysiologic measures seem to be tapping underlying dimensions which cross-cut current diagnostic boundaries to a greater or lesser degree depending upon the measure and the subject samples. Candidates for such underlying dimensions include illness severity, anxiety, arousal, attention, cognitive impairment, neuronal loss, intelligence and mood, to mention a few. Scores on these dimensions may predict drug response to a higher degree than diagnosis. The use of drug treatment response itself to validate subgroups of individuals identified by diagnosis is a common assumption in psychophysiology. Thus, patients who are responsive to a drug are assumed to have a different underlying illness than patients who are resistant. In clinical nosology, this assumption is not usually taken for granted. However, Brown and Hertz have recently argued for the need to pay more attention to identification and classification of patients along a neuroleptic response dimension. Diagnostic systems based on psychophysiological measures have been developed. One such system is "neurometrics" which involves comparing individuals on electrophysiological measurements, such as EEG power spectra, against a data base of normative values previously obtained from normal subjects. John et al. have shown that classifications based on neurometrics corroborate clinical diagnostic categories to a high degree, and can be used to independently validate current psychiatric nosology.(ABSTRACT TRUNCATED AT 400 WORDS)     

Toward an integration of interpersonal and biological processes: evolutionary psychiatry as an empirically testable framework for psychiatric research

Phenomenological, biological, and interpersonal aspects of psychiatric disorders lack an integrative empirical framework. In this paper evolutionary psychiatry is proposed as a meta-theory to integrate biological and interpersonal aspects of psychopathology. Pathological cognition, emotions, and behaviors may be examined according to specific biosocial goals originally pursued to increase the individual's inclusive fitness, similar to the ways that "normal" processes have been analyzed by evolutionary psychology. Sex-specific differences in prevalence rates and symptomatology of psychiatric disorders may also be better understood if divergent problems of adaptation for men and women in human evolutionary history are taken into account. Instead of mistaking the evolutionary approach for being deterministic and empirically untestable, it may rather be appropriate to provide a functional classification which adds to the contemporary psychiatric nosology through analysis according to specific conflicts of adaptation (at the ultimate level), the pursuit of biosocial goals, and proximate specifiers such as genetic, developmental, and interpersonal causes of disorders.     

Identification of the phenotype in psychiatric genetics

Summary Statistical procedures and molecular genetic techniques have attained a fine degree of resolution. Their ability to find disease genes has revolutionized medicine and raised hopes for breakthroughs in psychiatry. However, such breakthroughs may require an equally discriminating nosology. A psychiatric genetic nosology seeks to classify patients into categories that correspond to distinct genetic entities by addressing the problem of diagnostic accuracy: the degree to which a diagnosis correctly classifies people with and without a putative genetic illness. We review methods that deal with misclassification in genetic studies. These are clinical and epidemiological approaches that deal directly with how to define the observable manifestation of a putative genotype. We discuss two groups of methods: those that use known phenotypes and those that design new phenotypes.     

Toward a scientific psychiatric nosology. Strengths and limitations

A consensus is emerging that psychiatric nosology should become more "scientific." The application of the scientific method to psychiatric nosology has a number of important advantages, including (1) providing a clear criterion by which to evaluate nosologic proposals, (2) preventing rapid changes due to nosologic "fashions" not supported by research findings, (3) increasing the prestige and acceptability of our nosologic system to individuals outside of psychiatry, and (4) optimizing the reliability and validity of our diagnostic constructs. However, many critical issues confronting nosologists are fundamentally nonempirical and cannot be addressed by the scientific method. Examples of such issues include (1) disagreements about the proper construct for a psychiatric disorder; (2) the interpretation of results when different validators provide opposing answers; (3) defining how different syndromes must be to be considered subtypes of the same disorder, distinct disorders within the same overall category, or entirely independent disorders; and (4) the proper balance of reliability and validity. The optimal use of the scientific method in our nosologic process requires a recognition of both its strengths and its limitations.     

The DSM-V initiative "deconstructing psychosis" in the context of Kraepelin's concept on nosology

The revision process of the international psychiatric classification systems has started and is expected to result in new versions of the International Classification of Disorders (then ICD-11) and the Diagnostic and Statistical Manual (then DSM-V) in approximately 2014 and 2012, respectively. In the process of developing DSM-V, several research conferences jointly sponsored by the American Psychiatric Association, the National Institutes of Health, and the World Health Organization, are currently taking place. We will here focus on the impact that the DSM-V initiative "Deconstructing Psychosis" will have on the future of diagnosing a psychotic state, and how this may be viewed from a European context of Kraepelin's nosology of psychiatric disorders.     

Panic attacks. A review of treatments and pathogenesis

In the psychiatric literature, panic attacks have been considered as part of the clinical manifestations of anxiety neurosis, agoraphobia, functional cardiovascular disturbances, and the phobic depersonalization syndrome. Even though recurrent spontaneous panic attacks are described in these entities, the importance ascribed to them has been minor one. Therefore, panic attacks are poorly understood from a psycho-physio pathological point of view. In the past years, new trends in the nosology of psychiatric disorders have grouped the recurrent spontaneous panic attacks under the heading "panic disorder and agoraphobia with panic attacks." In this view, we present the results of the controlled pharmacological trials on patients complaining of panic attacks. Some relationships between panic attacks, panic disorder, and agoraphobia are discussed.     

Validity of reliability: comparison of interrater reliabilities of psychopathological symptoms

We have tested the stability of interrater reliability of psychiatric symptoms over a quarter of century using 2 rating scales. Interrater reliabilities of items of 2 psychiatric rating scales employed by 2 consecutive follow-ups were compared. Interrater reliabilites proved to be by and large stable. Interrater reliability depends on the standard deviation of the items scores. In addition to the traditional approach, a new statistical method for unifying the assessments from multiple raters is also presented. Using this method, we demonstrated that probabilities of correct ratings are higher in the absence of manifest symptoms, or in the presence of symptoms, as compared with cases characterized by middle scores. To interpret the relationships revealed in the setting of the experiment, we introduce for its theoretical designation the term "validity of reliability." It is recommended for evaluation of results of rating scales in the context of psychiatric nosology.     

Conceptual foundation of the operational diagnostic approach in psychiatry

Based on the pioneering work of Emil Kraepelin, Karl Jaspers, Kurt Schneider and representatives of logical empiricism, the basic principles of the operational diagnostic approach in psychiatry are described. Operational diagnostic systems like ICD-10 and DSM-IV aimed at a standardisation of psychiatric language which can be accepted by different schools in psychiatry. However, ICD-10 and DSM-IV should not be misinterpreted as "nosology" because they do not reflect a specific model of psychiatric diseases. The advantages of operational diagnostic systems as instruments for communication in a clinical and scientific context are limited by the fact that they disregard the subjective psychopathology. This dimension, however, deserves attention in clinic and research.     

Origins of DSM-I: a study in appearance and reality

The author traces the history of psychiatric nosology in the United States from its origins in the early nineteenth century to the introduction of DSM-I in 1952. Until World War I, psychiatrists were not interested in systematic classification, although they were concerned with diagnosis. The first official nosology, adopted in 1918, reflected the need to collect mental hospital data. The federal Bureau of the Census had a role in the development of this nosology in that it required such data. The publication of DSM-I marked an internal transformation that mirrored the growing dominance of psychodynamic and psychoanalytic psychiatry and the relative weakness of the biological tradition. This transformation occurred largely as a result of the lessons learned by psychiatrists during World War II. The author's basic argument is that nosology reflected not only psychiatric ideology but also other, external determinants at any given point in time.     

Academic psychiatry and the pharmaceutical industry

In the second half of the 19th century new drugs introduced by the pharmaceutical industry helped lead to the establishment of academic departments in psychiatry. Causal treatment of cerebral pellagra by nicotinic acid and cerebral syphilis by penicillin in the first half of the 20th century led to major changes in the diagnostic distribution of psychiatric patients. In the second half of the 20th century with the introduction of a rapidly growing number of psychotropic drugs, pharmacotherapy became the primary form of treatment in mental illness. Psychiatrists today perceive neuropharmacology as one of the basic sciences of psychiatry and psychopharmacology as the bridge between the mode of action and the clinical indications of psychotropic drugs. Pharmacotherapy with psychotropic drugs focused attention on the differential responsiveness to the same drug within the same diagnostic category. Yet, instead of re-evaluating psychiatric nosology and conducting research in psychopathology, a statistical methodology was adopted for the demonstration of therapeutic effectiveness in pharmacologically heterogeneous populations. Employment of consensus-based classifications and psychiatric rating scales in the clinical development of psychotropic drugs led to semi-finished products, which are prescribed indiscriminately. Replacement of single-center clinical trials by multi-center centrally coordinated clinical investigations led to the control of education in pharmacotherapy by the pharmaceutical industry. To separate education from marketing, the identification of the treatment-responsive forms of illness and the delineation of the therapeutic profile of psychotropic drugs are proposed with the employment of a new methodology, the "Composite Diagnostic Evaluation System." It is postulated that development of a pharmacologically valid psychiatric nosology with the employment of a "nosologic matrix" would provide the pharmaceutical industry with the necessary feedback to develop clinically selective drugs in mental illness and to break the impasse of progress in "translational research" in psychiatry.     

Depression and anxiety secondary to medical illness

Mind and body remain stubbornly one. The distinction between primary and secondary disorders respects this unity. The distinction between "reactive" and "induced" carry causal implications and suggest the former is psychogenic and the latter organic--both of which are probably premature conclusions. The diagnostician, free of the demands on the pathologist, can pursue the correct nosology committed to demonstrating, not the pathophysiology, but the presence of adequate diagnostic criteria. Whenever a secondary disorder meets full criteria it may warrant the same treatment accorded to the primary disorder. Whether the disease is major or minor may also be of clinical significance. Only further application of psychiatric nosology to medically ill patients can resolve these issues. Karajgi et al recently found that the lifetime prevalence of panic disorder in a sample of patients with chronic obstructive pulmonary disease was 8%. The only respectable offspring of neurotic depression in DSM-III-R is dysthymia. As with neurotic depression, dysthymia is not a condition thought appropriate for or responsive to antidepressant drugs. Clinicians dealing with depression in the medically ill think of depression itself as "serious," that is, major.     

Psychiatric side effects of non-steroidal anti-inflammatory agents

The nonsteroidal anti-inflammatory drugs (NSAIDs) are often used all over the world. Their psychiatric side-effects are rarely known. We report a case of indomethacin related depersonalization and have done a review of literature. We wanted to show the NSAIDs's side-effects. These are non specific, they can be either affective disorders, depersonalization states, hallucinations, or paranoid psychosis (which seems to be the most frequent). The symptomatology is easily suppressed, as soon as NSAIDs are stopped and/or psychotherapeutic symptomatic treatment is started. Different explanations are proposed: prostaglandin inhibition for the NSAIDs in general, indolic molecular structure (which looks like serotonin) for the indomethacin in particular which is the NSAID the most find in these side effects. There is several studies about the role of prostaglandin in psychiatry above all about schizophrenia. Some therapeutic essays were realized with prostaglandins precursors. The rest of the nosology is less studied.     

Karl Ludwig Kahlbaum (1828-1899)--a protagonist in modern psychiatry

Kahlbaum was one of the most influencial psychiatrists of the 19th century. He paved the way for Kraepelin and inspired the development of 20th century clinical psychiatry. With his work he contributed to new ideas in general psychopathology and in psychiatric nosology. He described "clinical state-course-entities" and developed the concept of "exogenous reaction types", which would later be known as the "Bonhoeffer-paradigm". Kahlbaum was also the first to differentiate between centripetal, intracentral and centrifugal psychic functions, which was later transformed into the "psychic reflex circuit" by Wernicke. The concept of organic versus non-organic psychoses proved to be a heuristically fruitful classification system even for modern psychiatry. Kahlbaum was the first German psychiatrist to describe several disorders and syndromes and to coin new psychiatric terminology for them, including paraphrenia, hebephrenia, catatonia and cyclothymia. These terms and their originally associated meaning are still in use today. Kahlbaum's ambitious scientific aim was to develop specific therapeutic strategies which were based on a methodologically and etiologically sound classification system.     

French perspectives on psychiatric classification

This article reviews the role of the French schools in the development of psychiatric nosology. Boissier de Sauvages published the first French treatise on medical nosology in 1763. Until the 1880s, French schools held a pre-eminent position in the development of psychiatric concepts. From the 1880s until World War I, German-speaking schools exerted the most influence, featuring the work of major figures such as Emil Kraepelin and Eugen Bleuler. French schools were probably hampered by excessive administrative and cultural centralization. Between the 1880s and the 1930s, French schools developed diagnostic categories that set them apart from international classifications. The main examples are Bouffée Délirante, and the complex set of chronic delusional psychoses (CDPs), including chronic hallucinatory psychosis. CDPs were distinguished from schizophrenia by the lack of cognitive deterioration during evolution. Modern French psychiatry is now coming into line with international classification, such as DSM-5 and the upcoming ICD-11.