Psychiatric diagnoses: the weak component of modern research

Kraepelin's dichotomy is built on Kahlbaum's large monograph (1) on the history and principles of the classification of psychiatric disorders. Kahlbaum proposed a classification based on symptoms, course and good vs. bad outcome (vecordia vs. vesania). Kraepelin's classification owes its enormous success to the clarity of his concepts and his lively and literary language. Later Kraepelin himself had doubts about a clear distinction between schizophrenia and manic-depressive insanity, stressing in 1920 (2) that "no experienced diagnostician would deny that cases where it seems impossible to come to a clear decision are unpleasantly frequent. Therefore the increasingly obvious impossibility of separating the two illnesses satisfactorily should arouse the suspicion that our approach to the question was wrong".

Kraepelin's concept was seriously shaken by Zendig's follow-up study of Kraepelin's own patients diagnosed as schizophrenic, a substantial number of whom were found to have a good prognosis (3). Zendig's interpretation that the diagnosis had been made incorrectly proved to be wrong, as shown by Lange's diagnostic check (4), and the dichotomous distinction was later disproved by Kick's reassessment of Kraepelin's cases, which documented a continuum at the symptom level between the two groups (5).

Multiple studies subsequently confirmed the existence of a group of conditions between schizophrenia and affective disorders, which were named intermediate psychoses (6), mixed psychoses (7), atypical psychoses, schizo-affective psychoses. Kretschmer (8) assumed that about half of psychotic patients suffer from mixed psychoses. Important longitudinal studies, starting with that conducted by Schüle (9), demonstrated the existence of cases beginning as manicdepressive and later turning into schizophrenia, as well as cases initially schizophrenic and later turning into manic-depressive disorder (10-13).

Many follow-up investigations demonstrated that schizo-affective patients can manifest, over their lifetime, manic, depressive, catatonic, hebephrenic and other psychotic (mainly delusional) syndromes, the course and outcome of which take an intermediate position between schizophrenia and affective disorders (14). In addition, clinical-genetic findings confirmed the continuum hypothesis by comparing the morbid risk ratio for schizophrenia vs. affective disorders among first-degree relatives of probands with a diagnosis of affective, schizo-affective (affect-dominant and schizo-dominant) or schizophrenic disorder (15).

It is highly probable that Kraepelin would have changed his dichotomous concept had he lived longer. Hence, those who still believe in that concept today may be called archeo-Kraepelinians rather than neo-Kraepelinians. There may be several reasons why Kraepelin's dichotomy has survived until now despite findings disproving it: a) Kraepelin's nosology was for a while the counterpart to the psychoanalytical view; b) by nature we prefer to think dichotomously; c) for obvious practical reasons, the important and influential diagnostic and statistical manuals (ICD, DSM) develop slowly, have to stick to discrete diagnostic classes and have to be conservative.

An early fundamental critique of the dichotomy was based on serious doubts about the existence of psychiatric entities defined by symptoms, course and outcome. The great antagonists of Kraepelin, Hoche (16) and Bumke (17), preferred a pure, descriptive syndromal approach and assumed that identical syndromes can have multiple causes (18), a concept which is of great relevance today. Mundt suggested a transnosological psychopathology (19) and van Praag proposed a functional psychopathology based on biological mechanisms, pointing out that "nosologomania" is a "disorder of psychiatry" (20). It is also an old story that drugs act on target symptoms or syndromes across disorders (21), although they are licensed for the latter. A book on psychopharmacology with such a syndromal approach was published in 1979 (22).

The great danger of the present operational diagnoses is that they are misperceived as well-established "natural" entities and that clinicians restrict their examinations and even their research to them. Examples are the widely used standardized interviews in epidemiology, which do not describe psychological and somatic symptoms comprehensively, but identify only whether or not symptoms meet a diagnostic scheme, with a serious inherent loss of information. This approach cannot question the diagnostic criteria themselves and is therefore unsuitable for developing the system further. Better measurements, as mentioned by Craddock and Owen, are badly needed and one can only agree with all their recommendations.

If treatment utility should be a main goal of classification, as Craddock and Owen suggest, therapeutic studies have to be much more sophisticated and more independent from the pharmaceutical companies' proximal interests. The minimized assessment and measurement of psychopathology in therapeutic studies has to be replaced by much more comprehensive symptom inventories, like those which were used some decades ago. Currently the goal and methods are usually set by the minimum requirements of the European Agency for the Evaluation of Medicinal Products (EMEA) or the Food and Drug Administration (FDA) for the marketing of new drugs and not by scientific or realistic practical targets. As a consequence, the results of many studies, especially those which are placebocontrolled, cannot be generalized and transferred into practice.