Psychopharmacology and the Classification of Functional Psychoses

By Thomas A. Ban and Bertalan Petho



Recent progress in epidemiologic and biologic research is responsible for a renewed interest in psychiatric diagnosis and classification. The new trend has received an impetus from the recognition that operationally defined diagnostic criteria are prerequisites for a valid comparison of epidemiological data from different language areas; for the identification of biological markers of disease and for the demonstration of the effectiveness of new psychotropic drugs. In addition to their importance for psychiatric research, diagnosis and classification are "necessary tools" for choosing suitable treatment and providing necessary "care and counselling" are to "the psychiatrically ill" (Helmchen, 1980).


Multi-Axial Classifications

A rationale for separating "etiology" from "symptomatology" was offered by Essen-Moller (1961). He contended that by assessing patients on two different, independent "axes," a number of combinations of syndromes and etiology would emerge which might not correspond to traditional (syndromatological) psychiatric diagnoses and thereby invalidate some of the old diagnostic hypotheses. By designing a model for a bi-axial system Essen-Moller Criteria Moller (1971) opened a new path leading to the development of multi-axial systems of diagnostic classifications in psychiatry (see Appendix I, Table I).

A changing attitude toward psychiatric diagnosis is reflected in the Mental Disorders section of the ninth revision of the International Classification of Diseases (ICD-9) of the World Health Organization (WHO, 1975, 1977). In ICD-8, etiological criteria were mixed with symptomatological, typological and topographic ones as well as with criteria relevant to the course of the disease (WHO, 1965, 1967), whereas in ICD-9, according to Helmchen (1980), there is an attempt to separate "symptomatology" from "etiology." However, because ICD-9 is a uni-axial classification, many of its diagnostic terms remain a mixture of different elements.

The first models of multi-axial systems of diagnostic classifications in psychiatry were developed independently by Ottosson and Perris (1973) and Helmchen (1975). They entailed four and five axes respectively. The four axes of Ottosson and Perris are "symptomatology," "severity," "etiology" and "course"; and the five axes of Helmchen are "symptomatology," "time," "etiology," "intensity" and "certainty" (see Appendix I, Tables II and III). Other important models of multi-axial classifications are those of Wing et al. (1968) and Strauss (1975). The four axes of Wing et al. are "psychiatric condition," "underlying cause or use or precipitating factor," "mental subnormality" and "additional physical illness or handicap”; and the five axes of Strauss are "symptoms," "previous duration and course of symptoms," "associated factors," "personal relationships" and "work function" (see Appendix I, Tables IV and V).

A significant, recent contribution to multi-axial psychiatric diagnosis is the third edition of the Diagnostic and Statistical Manual of the American Psychiatric Association (DSM-III, 1980). By its operationally defined diagnostic criteria and multi-axial system of evaluation DSM-III represents an important step towards a scientific approach to psychiatric diagnosis. Other important contributions in the development of operationalized diagnostic criteria are the St. Louis Criteria of Feighner et al. (1972), the Present State Examination Criteria of Wing, Cooper and Sartorius (1974), the Research Diagnostic Criteria (RDC) of Spitzer, Endicott and Robins (1978a,b), Taylor and Abram's Criteria (Taylor and Abrams, 1978; Taylor, Redfield and Abrams, 1981) and the Vienna Research Criteria of Berner and Katschnig (1983).


Empiricistic, Experimental and Nosological Approaches

In spite of the increasing sophistication in the differentiation of diagnostic categories within the traditional framework, research findings which have accumulated during the past decades strongly suggest that the classical nosological groups are only in part homogenous entities. This is reflected in the differential responsiveness within the same diagnostic category to the same psychotropic drug, and in the considerable variation of neurophysiological and biochemical measures within the same diagnostic category.

In the absence of well-identified etiology in most psychiatric disease, there are three approaches employed in differentiating biologically meaningful homogenous psychiatric patient populations: the empiricistic, the experimental and the nosological.

The empiricistic approach is based on the development of an assessment instrument, e.g., rating scale, that is constructed in a manner to include all known manifestations of a psychiatric disease, e.g., depression. It is assumed that by administering such a scale to large, clinically homogenous depressive populations and employing different statistical procedures, e.g., factor analysis, cluster analysis, multiple discriminant function analysis in the treatment of collected data, meaningful subtypes or diagnoses within a group of disorders can be obtained.

An alternative to the empiricistic approach is the experimental approach. It is based on biologic measures, e.g., neurophysiologic, bio-chemical, neuroendocrine. While it is hoped that some of these measures (biologic markers) will bring about a more meaningful classification of clinical psychopathology, it is commonly held that the meaningfulness of biologic markers is limited by the extent that they can be linked to a clinically identifiable diagnostic group.

The prototype of the third, or nosological approach is Kraepelin's (1896) three-dimensional model of classification, which was presented for the first time in the 5th edition of his textbook of psychiatry. Kraepelin's classification is based on three successive stages (dimensions) of psychiatric disease. In the first four editions of his monumental work, Kraepelin used a syndrome-oriented approach to the classification of mental illness. Beginning with the 5th edition he adopted the medical concept of psychiatric disease and shifted emphasis from the "pathological picture" to the "criterion of progress" (Pichot, 1983). According to Kraepelin "the necessity" for the shift in emphasis was brought about "by practical needs," by the "limitations of grouping on the basis of pathological pictures (Krankheitsbilder)," and by the recognition of the importance of criteria "which derive from the developmental stages, the course and the outcome of individual disorders."

Kraepelin's shift of emphasis from the cross-sectional picture to the course of illness had its origin in Kahlbaum's (1874) formulation of the notion of nosological entity. This was based essentially on Falret's (1864) contention that for a better understanding one has to learn about "the progression and the various stages of the natural form of mental disorders." For Falret a "natural form" of a disease "implies a well-defined (natural) predictable course," which in turn "presupposes the existence of a natural form of disease with a specific pattern of development."

An alternative to the three-dimensional model is the four-dimensional model of nosological classification. This is based on all successive stages of psychiatric disease. Leonhard's (1957, 1979) classification of "endogenous psychoses" is based essentially on a four-dimensional nosological approach.


From One Dimensional to Four Dimensional Classifications

In the psychiatric literature the terms "axes" and "dimensions" are used interchangeably in an unconventional manner referring to different aspects or components of the disease in an arbitrary manner (Mombour, 1975). With the term axes, emphasis is on the independence of the components; while with the term dimension, the emphasis is on relationships among the components in a time sequence. Hence, the four dimensions, or rather developmental stages include cross-sectional psychopathology (1st dimension or 2nd developmental stage), onset-etiology (2nd dimension or 1st developmental stage), course of illness (3rd dimension or 3rd developmental stage) and outcome (or end-state) features (4th dimension or 4th developmental stage).

Inclusion of the entire disease from beginning to end is a prerequisite for a comprehensive picture which should provide for a better understanding of the nature of psychiatric illness. In keeping with this is Kahlbaum's (1874) notion that "only an inclusive and general use of the clinical method can advance psychiatry and increase understanding about the pathological process involved in mental illness." Corresponding with this notion are the findings that by encompassing an increasing number of developmental stages of the disease, the heterogenous population of psychiatric patients can be separated into increasingly more homogenous and differentiated diagnostic groups. Thus, by employing a two-dimensional approach, the one-dimensional concept of unitary psychosis-vesania (Neumann, 1859; Griesinger, 1845, 1867, 1876), could be separated into two psychoses, i.e., exogenous and endogenous.

Introduction of the third dimension opened the possibility of separating patients within the population of exogenous psychosis into organic (including "symptomatic psychosis" and "psychosis associated with coarse brain disease") and psychogenic (also referred to as reactive) psychoses; and to separate patients within the population of endogenous psychosis into schizophrenic (dementia praecox) and affective (manic depressive) psychoses. Since psychogenic and endogenous psychoses are considered to be sui generis, primary psychiatric illnesses, they are commonly referred to as "functional psychoses" to separate them from the nonspecific psychiatric disorders associated with neurological and/or other systemic diseases and from developmental inborn and/or learned anomalies such as "mental retardations" and "psychopathic personalities" (Schneider, 1925).

Finally, introduction of a fourth dimension, and with it a structural approach, has made it possible to separate patients within both the schizophrenic and the affective psychoses into two major diagnostic groups, i.e., nonsystematic and systematic. In addition, the four dimensional model of psychiatric diagnosis has focused attention on acute and chronic delusional psychoses, a population between the reactive and endogenous psychoses; and on cycloid psychosis, a population between the affective and schizophrenic psychoses (Table 1). It has also brought to attention numerous subtypes within each group of the major diagnoses (Figure 1).


Proposed Classification: Supporting Data

The proposed four-dimensional classification is firmly rooted, although not exclusively based, in cross-sectional psychopathology, extending its boundaries beyond experiential phenomenology into behavior, performance and holistic (Gestalt) characteristics of the disease (Ban, 1982; Conrad, 1958; Pethö, Tolna and Tusnady, 1979; Petrilowitsch, 1969). It employs a decision tree model. Accordingly, alternative decisions are based not merely on a given set of knowledge (cross-sectional psychopathology) and a logical process moving within one set of data. It also follows the evolution of the subject (illness) under study in time (Pethö, 1984b).

In the course of this process first, endogenous and exogenous (reactive) psychoses are separated on the basis of the relative importance of a precipitating event in activating the disease. Subsequently, psychopathological syndromes are identified on the basis of an analysis of psychopathological forms with consideration of their content. The formal characteristics of the course of the disease, such as rhythmicity, periodicity, polarity, etc. are distinguished from the contents of the course, such as time spent in hospital, intensity and duration of pharmacotherapy etc. (Pethö, 1984a). Finally, the outcome characteristics are utilized in the validation of diagnoses (Pethö, 1977, 1984b).

The diagnostic system proposed is undoubtedly more detailed and subtle than other diagnostic systems used in psychiatry today. It still must be shown, however, that its diagnostic subtypes are biologically more meaningful categories than the diagnostic types described in ICD-9, operationally defined by DSM-III, and/or identified by the various diagnostic systems employed in psychiatric research.

In favor of the contention that diagnoses within the four dimensional model represent biologically more homogenous populations (than diagnoses within the three dimensional model) are clinical psychopharmacologic findings (Astrup, 1959; Astrup and Fish, 1964). These findings suggest that in schizophrenic patients classified based on Leonhard's (1957, 1979) system, therapeutic responsiveness to neuroleptics is considerably more predictable than in schizophrenic patients classified on the basis of other diagnostic classifications.

By employing Leonhard's classification, Fish, as early as 1964, found that 117 out of 123 nonsystematic schizophrenic patients (95%) showed a favorable therapeutic response to neuroleptics, while only 289 out of 351 systematic schizophrenic patients (69%) showed a similar response (Fish, 1964a). The most important findings, from both a practical and a theoretical point of view, however, was that among nonsystematic schizophrenic patients, the favorable therapeutic response was rated marked to moderate in 79% of treatment responsive patients, while among systematic schizophrenic patients it was rated marked to moderate in only 23%.

It was also noted that, among the nonsystematic patients, those suffering from periodic catatonia responded less favorably than patients with affect-laden paraphrenia and especially cataphasia. Among the systematic patients, therapeutic responsiveness was not evenly distributed among the three major classes of psychoses. Thus, while a moderate or marked therapeutic response was seen in as high as 40% of the patients belonging to one or another subtype of the systematic paraphrenias, a similarly favorable response was seen only in 23% of the patients belonging to one or another subtype of the systematic hebephrenias and 0.9% of the patients belonging to one or another subtype of the systematic catatonias.

That Leonhard's system of classification might identify biologically meaningful categories is also supported by preliminary findings regarding tardive dyskinesia in a multinational survey of 768 chronic hospitalized schizophrenic patients (Ban, Guy and Wilson, 1984a). In this survey the overall prevalence rate of tardive dyskinesia for the population was 11% when determined by clinical judgment and 13% when determined by the Research Diagnostic Criteria for Tardive Dyskinesia (Schooler and Kane, 1982).

However, by employing Leonhard's diagnostic system, prevalence rates were found to be significantly lower in the therapeutically more responsive non-systematic group (4.3%), than in the therapeutically less responsive systematic group (13.3%). The manneristic subtype of the systematic catatonias attained a prevalence rate of 28% and the silly subtype of the systematic hebephrenias attained a prevalence rate of 53%. In the expansive and confabulatory subtypes of the systematic paraphrenias, tardive dyskinesia was not encountered at all (Guy, Ban and Wilson, 1985).

Because there is no indication that the action mechanism of neuroleptics would be different in patients belonging to different diagnostic groups, it seems likely that in the development of tardive dyskinesia, the biology of the host also plays an important role. Furthermore, because there is no indication that patients with different types of schizophrenia as classified by the ICD-9 or DSM-III develop tardive dyskinesia differentially to neuroleptics, the preliminary findings, of differential occurrence within Leonhard's classification favor the contention that diagnoses based on Leonhard's system, provide for biologically more homogenous populations than diagnoses based on other systems of classification.


Use of Terms: Psychosis, Endogenous, Psychogenic

The four-dimensional model of psychiatric diagnosis has evolved in the course of systematic research on "psychotic" patients. While the only purpose of these studies was to differentiate clinically meaningful groups within the psychotic population, the findings also indicated that the concept of psychosis should not be based on the intensity of psychopathological symptoms. If severity of illness is the basis of the distinction, one and the same disorder may appear in psychotic and non-psychotic forms. Because of this in the proposed classification Schneider's (1950, 1959) definition of psychosis is adapted. Thus, the term psychosis designates psychopathological syndromes resulting from disease and regardless of the intensity of the pathology. In this respect the proposed classification is in keeping with ICD-9 and is at variance with DSM-III in which according to Pichot (1983) intensity is of primary importance in the definition.

In the proposed classification the term psychosis is retained to separate disease-related psychopathological syndromes from disorders of personality which, according to Schneider represent psychic abnormalities, i.e., statistical deviations from the social norm (normal) with which they are "united by a series of imperceptible transitions" (Pichot, 1983). Thus, for Schneider, psychoses, in contradistinction to personality disorders, are always of somatic origin, regardless of whether a somatic etiology has been identified. It is within this frame of reference that the term "functional psychosis" is used in this monograph.

Within the conceptual framework of this monograph, endogenous psychoses are perceived as being the result of a seemingly spontaneous interaction between endogenous, assumedly genetic factors and brain structures; while reactive (psychogenic) psychoses are perceived as the result of a precipitated interaction between endogenous, assumedly genetic factors and brain structures. Considering that the essential difference between the two psychoses is the presence or absence of a need for an exogenous "psychological" factor to precipitate the psychosis, one may entertain the possibility of replacing the terms endogenous and psychogenic psychoses by the terms endogenomorphic and exogenomorphic psychoses respectively.

Moreover, if subjects with deviant (abnormal) personalities would be referred to as "psychopathic personalities" as done by Schneider (1923, 1958), the term "psychosis" could be replaced by the term "disorder," as used in the DSM-III. However, if the term "endogenomorphic," is used, one must remember that the same term has been used by Klein (1973) in relation to depressive illness that mimics the characteristics of endogenous depression and which is usually responsive to a wide range of somatic interventions; and also by Berner (1982, 1983), in relation to axial syndromes which might indicate schizophrenic, manic or depressive developments. Although the terms exogenomorphic and endogenomorphic might be more appropriate than the terms presently in use, they will not be employed in this monograph.

On the other hand, the term psychosis will be retained in recognition of the distinction between psychiatric illnesses and developmental anomalies and within psychiatric illnesses between anxiety disorders (neuroses) in which patients have good insight and psychoses in which patients have no insight, even if they recognize to some extent, the nature of their pathological experiences. It is this latter group (psychoses) which will be the subject matter of this volume.


Table I

Figure I