Thomas A. Ban
Neuropsychopharmacology in Historical Perspective
Psychopharmacology and the Classification of Functional Psychoses
In this monograph the historical development of a four-dimensional classification of functional psychoses was outlined. The presentation was restricted to the evolution of concepts with emphasis on the extension of the diagnostic information from cross-sectional psychopathology to all developmental stages of psychiatric illness.
The proposed classification is firmly rooted in cross-sectional psychopathological symptoms. It differs from syndromatological classifications in that the clinical syndromes are not studied in isolation but in the nosological context of the total longitudinal picture of the illness. The nosological entities described do not fulfill all the criteria of a "disease" (Jaspers 1959, 1963). However, a nosological approach was employed to prevent confounding the biological correlates of any particular stage (cross-sectional syndrome) of a disease with the central biological mechanism of the illness.
Inclusion of "psychogenic" psychoses (Faergeman 1963) represents an extension of the original concept of functional psychoses from exclusively "productive" (endogenous) to "reactive" illnesses. In "productive" illness, "a process takes its course, leading to a progressive alteration in the psychic constitution," without external cause. In "reactive" illness, "a preexisting abnormal constitution reacts in an abnormal way to external events only to revert to its earlier state when these events cease" (Jaspers 1974). However, the fact remains that even in case of psychogenic (reactive) psychoses only "the contents of the pathological states are meaningfully connected with the initial experience" (Jaspers 1913, 1974). In other words, understanding these disorders on the basis of a traumatic life event relates to the content of these psychoses but does not extend to understanding their forms.
The adoption of Leonhard's (1957) subtypes in the classification of "endogenous-productive" illnesses is based primarily on clinical observations. In favor that the subtypes are valid diagnoses are the findings that in their course functional psychoses display increasingly differentiated features. This is at variance with Conrad's (1958) contention that progressive stages of one and the same illness are represented in the different syndromes (Fish 1961). None of these observations exclude the possibility that a state of over-arousal (Kornetsky and Mirsky 1966; Weil-Melherbe and Szara 1971) might play a central role in the pathophysiology of all subtypes or developmental stages of schizophrenias and desynchronization of the circadian rhythm (Halberg 1968; Mellerup and Rafaelsen 1979; Pflug and Tolle 1971) of all affective disorders.
General paralysis, a disease produced by the effects of treponema pallidum in the brain, may appear as several distinctly different syndromes. Because of this, general paralysis has become a specter against "subtyping" in psychiatry. Within a three-dimensional model of diagnosis all patients with the same diagnosis and regardless of their early manifestations, display a similar syndrome, i.e., dementia. In other words, it is dedifferentiation which results in dementia, the common final syndrome in all patients with general paralysis, a systemic neurological disease; while it is differentiation which results in subtypes, or distinct syndromes in patients with functional psychoses. Consequently, diagnostic evaluation of these disorders must proceed in a step-wise fashion and encounter an increasingly larger proportion of the illness, i.e., onset, cross-sectional syndrome, course and outcome.
Description of psychopathological symptoms is usually the first step in diagnostic evaluation. This is followed by the identification of “psychosyndromes” which are based on the profiles of simultaneously present psychopathological forms. Considering that localization of psychopathological events (symptoms) in the brain has failed in spite of many attempts, a purely syndrome-based approach to classification of psychiatric disorders has little to offer concerning an understanding of these illnesses.
An alternative to the syndrome-based approach to the classification of psychiatric disorders is the nosology-based approach. By accepting the "nosological postulate" it is assumed that each psychiatric illness, characterized by a specific psychopathologic syndrome, has a characteristic course with a predictable outcome even if, for the time being, its etiology is not known.
Analyses of cross-sectional psychopathological syndromes in the different psychiatric illnesses have brought to attention distinct differences in the affected psychopathological structures. These differences appear in the general and special characteristics of the different disease pictures. Accordingly, manifestations related to systemic (organic) disease display psychopathological symptoms which are primarily related to “integrational” functions, such as "disorders of consciousness,” "memory impairment," "disorientation" and/or "deterioration of personality," while manifestations of functional (psychogenic and endogenous) psychoses display psychopathological symptoms which are primarily related to "perceptual-cognitive,” "relational-affective" and "motor-adaptive" functioning. In the affective disorders psychopathological symptom development is related to mood (holothymic or mood congruent); and in both affective and cycloid disorders psychopathological symptoms related to cognitive, affective and adaptive functioning are in harmony, i.e., in keeping with each other. The same does not apply to schizophrenic disorders, where symptom development is unrelated to mood and is based on catathymic (emotional) mechanisms and where psychopathological symptoms related to cognitive, affective and adaptive functioning are dissociated, i.e., split, from each other. Nevertheless, in both schizophrenic and affective disorders, nonsystematic illnesses are characterized by multiform (polymorph) and systematic illnesses by simple (monomorphic) clinical pictures.
Among the functional psychoses, delusional psychoses, paraphrenic schizophrenias and confusion psychoses display psychopathological symptoms which are primarily related to perceptual-cognitive functioning. Other diagnoses with psychopathological symptoms related to perceptual-cognitive functioning include affect-laden paraphrenia (delusions with strong delusional dynamics), psychogenic paranoid psychosis (ideas of reference), unproductive euphoria and harried depression (restricted thinking or poverty of thought), hypochondriacal euphoria and hypochondriacal depression (hypochondriasis), confabulatory euphoria (confabulations) and suspicious depression (suspiciousness).
Among the endogenous psychoses, both affective and cycloid psychoses display psychopathological symptoms which are primarily related to relational-affective functioning. However, in affective disorders hyperthymic (elated) or dysthymic (depressed) mood is the dominant clinical feature, while in cycloid psychoses it is perplexed mood, i.e., a mood of puzzlement or uncertainty. Other diagnoses with psychopathological symptoms related to relational-affective functioning include psychogenic affective psychoses (exaltation or depression) and the systematic hebephrenias (emotional indifference and blunted effect).
Finally, among the schizophrenic psychoses, systematic catatonias, cataphasia and periodic catatonia display psychopathological symptoms which are primarily related to motor (including speech)-adaptive, functioning. Other diagnoses with psychopathological symptoms related to motor-adaptive functioning include motility psychosis (hyperkinesia or hypokinesia), harried depression (restlessness), autistic hebephrenia (autism) and eccentric hebephrenia (soft mannerisms).
It remains to be seen to what extent the cross-sectional psychopathological syndromes will fulfill expectations regarding predictability of course and outcome of a psychiatric disease. But even if such expectations are fulfilled, the question remains whether corresponding changes in the brain with the proposed nosological categories can be identified by the presently available biochemical, neurophysiological and/or brain imaging techniques.
Form of Onset
Cross-sectional syndromes are based on the simultaneous presence of different psychopathological forms. Considering that only the content of these manifestations are understandable through patient developmental history, relevant anamnestic information for nosological diagnosis is restricted to the description of the onset (acute, subacute or chronic) of the illness and information, whether criteria of an exogenous reaction, biological reaction in case of systemic disease and psychogenic reaction in case of psychic trauma, are fulfilled.
Because form of onset provides for only three possibilities (acute, subacute and insidious), different forms of onset become meaningfully interpretable only with consideration of information regarding subsequent developmental stages of the disease. However, in case of functional psychoses, an insidious onset indicates systematic schizophrenic disease, although in the differential diagnosis chronic interpretative delusional psychosis needs to be entertained. Furthermore, while a biological reaction with few exceptions, produces psychopathological symptoms indicative of organicity, such as disorder of consciousness, memory disturbance, disorientation and/or deterioration of personality, a psychological reaction may display psychopathological features resembling organic (dissociative) or endogenous (affective or paranoid) syndromes. Consequently, for a diagnosis of psychogenic affective or paranoid psychosis consideration needs to be given to the third developmental stage or the course of the disease.
Course of Illness
In nosological diagnoses there is a shift in emphasis from developmental history to course of illness, i.e., whether the disorder follows a recurrent, possibly rhythmic, or continuous, possibly downhill course. However, neither “recurrent” and “rhythmic” nor "continuous" and "downhill" should be interchangeably used, because "rhythmic recurrence” is restricted to cycloid and affective psychoses and the nonsystematic schizophrenias, while a "continuous downhill" course is present only in the systematic schizophrenias and chronic delusional psychoses.
Recognition of the importance of the unipolar-bipolar dimension in relationship to mood states, including also other aspects of relational-affective and motor-adaptive functioning, opened the possibility for the separation (within the affective psychoses) of unipolar and bipolar illnesses. It led to the recognition that not only affective psychoses, but also cycloid psychoses and nonsystematic schizophrenias, may follow a unipolar or bipolar course. Furthermore, recognition of the relationship between disease picture and course of illness, multiform picture-bipolar course and simple picture-unipolar course, prompted re-evaluation of cross-sectional psychopathological syndromes. This in turn yielded to the identification of numerous subtypes within the schizophrenias and the affective psychoses.
Outcome and End-State
Outcome is the final developmental stage of psychiatric illness and the ultimate validation of four-dimensional diagnoses is through their "outcome features.” Outcome features range from full "recovery" from the illness to residual psychopathology. In between the two extremes are full “remissions” between episodes of the illness and subclinical manifestations, such as maladjustment and/or personality changes. In contradistinction to the conventional, we have used the term "residual," to denote irreversible "end-states,” characterized by distinct psychopathological syndromes (subtypes). These develop in disorders with a continuous course, such as systematic schizophrenias and chronic delusion psychoses. The opposite to residual psychopathology is full recovery, a prerequisite for a final diagnosis of psychogenic and acute delusional psychoses. Full recovery, however, does not imply protection against recurrence of the same or another psychiatric illness.
Full remission is the characteristic outcome feature of affective and cycloid psychoses. The "symptom" free periods (remissions) are between the symptomatic episodes in disorders which follow an episodic-recurrent course. While as a rule residual psychopathology is absent, it is not infrequent to see personality changes after recurrent episodes of cycloid psychoses and maladjustment after prolonged episodes of affective disorders, e.g., euphorias, depressions.
Although nonsystematic schizophrenias follow a recurrent episodic course, full remissions are not encountered between episodes. Instead, there are personality changes with maladjustment and, not infrequently, distinct psychopathological symptoms.
Effect of Pharmacotherapy
There is substantial evidence to believe that among the different treatment modalities for the functional psychoses, pharmacotherapy is significantly superior to other treatment modalities. Still, the question remains: to what extent has the introduction of psychotropic drugs changed the four developmental stages of the different illnesses?
Insofar as form of onset, i.e., the first developmental stage, is concerned, there is no reason to believe that it has been affected by the introduction of psychotropic drugs. Primary prevention is still outside the scope of clinical psychopharmacology. There is no indication that the onset of functional psychoses can be prevented and/or that the form of the onset modified by any of the available psychotropic drugs.
The same applies also to outcome that has not shown essential change that can be attributed to the introduction of modern pharmacotherapies. Accordingly, residual psychopathology remains the characteristic outcome of systematic schizophrenias and chronic delusional psychoses and full recovery of psychogenic and acute delusional psychoses. There are full remissions between recurrent episodes of affective and cycloid psychoses and partial remissions between recurrent episodes of unsystematic schizophrenias. In spite of all pharmacotherapeutic advances, however, recurrent episodes may still result in personality change in cycloid psychoses, maladjustment in affective psychoses and residual psychopathology in unsystematic schizophrenias.
Pharmacotherapy-induced changes are restricted to the second and third developmental stages, i.e., cross-sectional psychopathology and course of illness, in the functional psychoses. During the second developmental stage (cross-sectional syndrome), it is well established that neuroleptics, cyclic antidepressants and lithium salts can significantly decrease the intensity or severity of schizophrenic, depressive and manic clinical manifestations. In case of episodic disorders, they can also shorten the duration of the active phase of manifest psychopathology. There are only indications, however, that the same drugs during the third developmental stage (course of illness) can significantly increase the duration of the interval between episodes and maintain patients in remission. Considering that not all patients respond equally well to treatment and that treatment and especially maintenance-prophylactic treatment with these drugs can result in chronic adverse effects, efficacy studies with psychotropic drugs should be designed in a manner that they could identify the therapeutically responsive population within the different diagnostic groups. It may also be necessary to shift the emphasis of efficacy studies from the second to the third developmental stage, that is, from control of symptoms to maintenance of remission.
Irrespective of their impact on treatment, the new drugs have focused attention on the heterogeneity of psychiatric populations within the generally accepted (ICD-9 and DSM-III) diagnostic categories. Also, within each diagnostic group some patients respond while others remain refractory to the same therapeutic approach. To date there are no established biological markers for any of the diagnoses and there are no indications that any of the accessible biochemical and/or neurophysiological measures will increase the biological homogeneity of diagnostic groups in terms of therapeutic responsiveness to psychotropic drugs.
We do not necessarily believe that in the proposed classification specific cerebral changes will show greater correspondence (parallel) with diagnosis-specific changes in the different psychopathological structures than in other currently used classifications. We are more inclined to agree with Jaspers' early (1910, 1963) contention that all research "up to now has only brought us closer to finding such parallel events, but they have nowhere actually been found.” On the other hand, we firmly believe that the psychopathological syndromes are integral parts of distinct psychiatric illnesses within the functional psychoses. We also believe that a careful analysis of psychopathological syndromes within the context of their developmental pattern of onset, course and outcome, can provide for biologically more homogeneous populations than the populations derived by any other methods.
We hope that in the proposed classification the conceptual development of different illnesses, subsumed under functional psychoses, is properly reflected. The conceptualizations presented evolved in the course of a historical process which has integrated numerous clinical observations into distinct clinical pictures. Because the diagnostic groups have not been generated by generally accepted empirical and/or experimental methods, their validity will have to be established in carefully designed clinical research.
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July 1, 2021