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Monday, 29.05.2017

THOMAS A. BAN: TOWARDS EDUCATION IN THE HISTORY OF NEUROPSYCHOPHARMACOLOGY

Part XI. Educational Program
1.     Psychopathology

By the end of 2015, the Cordoba Unit was transformed into INHN’s Central Office and on January 4, 2016, the Central Office started to post an Educational Series to complement the weekly postings of INHN Website Communications, which has been in operation since April 3, 2013.

On September 1, 2016, INHN Education was launched with a course by Carlos Morra and Ernst Franzek on Psychopathological Symptoms. The mission of INHN is the facilitation of communication between neuropsychopharmacologists of different generations and professional backgrounds.  The objective of INHN Education is to render the necessary historical information accessible in order that the Network fulfill its mission.

Background to the 1st course:

Psychopathology: Historical Development

The roots of "psychopathology" can be traced to Galen's (131-201 AC) recognition of  "animal faculties" which are comprised of "sensation," "cerebration via imagination," "cogitation," "memory" and "voluntary motions." These “mental faculties” provide an elementary conceptual framework of mental activities which are selectively affected in the different mental disorders.

The origin of the assumption of an intimate relationship between "psychopathological symptoms" and "mental illness" is in Galen's postulations that "symptoms follow the disease as shadow follows its substance," and the "signs of a disease show what the disease is and how it will end." By suggesting a relationship between symptoms and disease, with the disease defining its symptoms  to  the extent that it becomes possible to determine ("diagnose") from  the  symptoms  what  the  disease is, and  how it will end (prediction), Galen formulated the first concept of "disease" that set the stage for a development in which “medicine” became a distinct clinical discipline (Garrison 1929).

In spite of Galen’s recognition in the 2nd century that “symptoms follow disease as a shadow its substance”, development of “psychopathology” began only in the mid-19th century. The term first appeared in Ernst Feuchtersleben’s 1845 textbook and throughout the second half of the 19th century it was used as a synonym for psychiatry. During these years, the vocabulary of psychopathological symptoms steadily grew. Esquirol (1838) divided false perceptions into “illusions” (distortion or misinterpretation of real perception) and “hallucinations” (perceptual experiences without corresponding stimuli in the environment); Griesinger (1863) distinguished between “pale (pseudo) hallucinations” (that appear in the inner subjective space and can be controlled voluntarily) and “true (real) hallucinations” (usually referred to simply as hallucinations); and Wernicke (1981-3) separated  “dysmnesia” (memory impairment) from “dementia”  (personality deterioration).

Development of "psychopathology" received a strong impetus in the early years of the 20th century through Karl Jaspers' recognition of the distinctiveness of the "case history," or “nosography,” i.e., the "history determined by illness," from the "life history” or “biography,” i.e., the history determined by life experiences. It was Jaspers’ examination of the nature of this distinctiveness, with the employment of "understanding psychology," i.e., "empathy" and "introspection," that lead to the separation of "disease process" responsible for the "case history" that is inaccessible to understanding by "meaningful connections" from “personality development” that is accessible  to understanding by “meaningful connections.” Personality development has its primary source in a specific "anlage or disposition" which "grows, evolves and absorbs in a continuous sequence of the changes brought about by respective age epochs," whereas the "disease process" intervenes and interrupts "personality development" by becoming superimposed on and intervening with it. Jaspers seminal paper on the distinctiveness of “disease process” from “personality development” was published in 1910.

            The signal difference between “development” and “process” is that "personality development" is understandable by "empathy" and/or "introspection" as it  is based  on   "meaningful  psychic  connections" ("genetic understanding")  in which  one "psychic event" arises from another, whereas the “disease process" is not. As a "stranger who has intruded into the understandable development of the personality," the "disease process breaks the continuity of meaningful connections of psychic life and interferes with comprehension.” Thus, “personality development” is the subject matter of "understanding psychology," the field of "psychodynamics," whereas “disease process” is the subject matter of "explanatory psychology" that deals with "causal connections of psychic life" formed repeatedly and with some regularity, which are not amenable to "genetic understanding,” but might be explained by heredity and/or environmental factors.

In his further exploration of the distinctiveness between "process" and "development," Jaspers examined the "symptoms" and "signs" in which "mental pathology" was expressed; and it was the information collected in the course of this examination that lead him to hypothesize a relationship between specific illness and particular "symptom" displays.

Psychopathology became a discipline to provide a foundation for psychiatry with Jaspers’ observation that in different psychiatric diseases patients process (in their brain) and consequently perceive the same “content” (information) in different “forms.”  His recognition of the relationship between the ”forms” in which information (“content”) is perceived by patients  and their  illness led to the birth of “phenomenological psychopathology” (phenomenology), the branch of psychopathology that deals with “abnormal subjective experiences of individual psychic life.” It also lead to the consolidation of his separation of “psychiatric disease process” that is displayed by “abnormal forms of experiences” from “abnormal personality development” that is displayed by behavior that deviates from the statistical norm.   

Within Jaspers' (1913) frame of reference, "psychiatry is a clinical practice" whereas "psychopathology" is a "science" with the explicit purpose of generating new knowledge and "to recognize, describe and analyze general principles rather than individuals." The information obtained by psychiatrists ("clinicians") on the mental life of their patients is complex. The "individual momentary experience" is "woven from a number of phenomena" and the "conscious psychic life" is in a "constant flux" of entangled clinical pictures in a "total relational context." It is the task of the "psychopathologist," the "scientist," to disentangle this complex material: to break it into distinct, clearly definable concepts, i.e., symptoms and signs, which can be communicated and used in the formulation of "laws and principles" (relevant to "pathologic psychic realities"), and in the demonstration of "relationships" between "mental illness" and "psychopathologic symptoms" (Ban 2013, 2016).

In his original formulation, Jaspers defined "psychopathology" as the scientific discipline concerned with the entire field of "pathologic psychic reality," i.e., with every "conscious pathological psychic event," which can be rendered "intelligible by a concept of constant significance."  In keeping with this broad definition, the scope of "psychopathology" in his General Psychopathology extends from the "subjective   phenomena   of   morbid   psychic life" ("phenomenology") through the "objective performance changes" ("performance psychology") and "somatic accompaniments of psychic morbidity" ("somatopsychology") to the "synthesis of disease entities" ("nosology”) and the "social and historical aspects of the psychoses and personality disorders."

As time passed, the all-embracing discipline of "psychopathology” was split into several distinct areas of research. First, "nosology," the field of research concerned with the "synthesis of disease entities" and the "classification of mental illness," was separated from "psychopathology" by the distinctiveness of its methodology, i.e., "synthesis" versus "analysis."  Later on, "abnormal psychology," the discipline in which "abnormal mental phenomena" are perceived and understood in terms of deviations from the statistical mean (norm) and accepted as normal within the subject's social background, was separated by the distinctiveness of its frame of reference, i.e., social-statistical versus biological-medical. Gone with "abnormal psychology" was, to a great extent, "performance psychology" and "somatopsychology," with the scope of "psychopathology" becoming increasingly restricted to "phenomenology," or more precisely "phenomenological psychopathology," the clinical elaboration of Jaspers "phenomenology" by the Heidelberg school of psychiatry.

The term "phenomenology" was adopted by Jaspers from Husserl, but aside from the term "phenomenological psychopathology," has nothing in common with Husserl's "phenomenology," a philosophy based on the assumption that "phenomenology," i.e., the "study of subjective experience of psychological events," is the science which preceded and governs all other sciences. Phenomenological psychopathology is also distinct from Binswanger's "existentialist interpretative psychology," in which "existential –phenomenological-- analysis" is used to reformulate "morbid psychic experiences" in terms of Heidegger's "existentialist  philosophy," on  the  basis  of  the presumption  that  the  formulation  of  "morbid psychic experiences"  within the frame of reference of Heidegger's philosophy would  render  the "pathologic realities" understandable.

In variance with Husserl, for Jaspers "phenomenology" was simply a "science" dedicated to the study of the "subjective phenomena of morbid psychic life" and not the "primordial science,” a methodology to render the "pathologic realities" accessible, and to break the complex "pathologic realities" into communicable concepts. And, in variance with Binswanger, for Jaspers, “phenomenology” was a clinical research method used to study and to relate the concepts of "pathologic realities," and not a means to understand the "pathologic realities", to mental illness.

In “phenomenological psychopathology” (“phenomenology”) it is not the subject matter, the information (“content”), the patient talks about, but how (“form”) the patient talks; and it is not the “somatic (hypochondriacal) complaints” (“content”), but the form of how these complaints are experienced by the patient, e.g., “bodily hallucinations” (somatic experiences without corresponding stimuli in the environment), “obsessive ideas” (ideas that persist against one’s will), “hypochondriacal delusions” (false beliefs based on a priori evidence), that are relevant to diagnosis. Even in case of “delusions,” a “content disorder of thinking” that signals the presence of an ongoing psychiatric disease (“psychosis”), it is not the “content“ of the “delusions,” such as “delusions of reference,” “delusions of love,” “delusions of persecution,” etc., but the “form” in which the “delusion” appears,  i.e., a “sudden delusional idea” (a delusional idea that appears to be fully formed),  a “delusional perception” (a delusional meaning attributed to a normally perceived object),  that is relevant to the abnormality in the processing of signals by the  brain that differentiates one psychiatric disease (process) from another. It was on the basis of  “phenomenological analyses” that, in 1920, Kurt Schneider distinguished between “vital depression,”  a disease, from the “other depressions,” and separated “personality disorders,” displayed in “abnormal variations of psychic life,” the subject matter of “abnormal psychology,” from “psychoses” (mental disorders), displayed in “abnormal forms of experiences,” the subject matter of “psychiatry.”

During the years from 1918 to 1933 a group of psychiatrists that included Hans Gruhle and Wilhelm Mayer-Gross in Kurt Wilmanns’ department of psychiatry at Heidelberg University in Germany, spearheaded “phenomenological analyses” in psychiatric patients (Shorter 2005). Their effort yielded a vocabulary that includes distinct words (symptoms) from pathologies of “symbolization,” such as “condensation” (combining diverse ideas into one concept) and “onematopoesis” (building new phrases in which the usual language conventions are not observed), to pathologies of “psychomotility,” such as “ambitendency” (the presence of opposite tendencies to action) and “parakinesis” (qualitatively abnormal movements). In “phenomenology,” “dysphoria,” the negative pole of “vital emotions” is distinguished from “dysthymia,” the negative pole of mood; “psychomotor retardation,” the experience of a spontaneous slowing down of motor activity, is distinguished from “psychomotor inhibition,” the experience of slowed down motor activity, etc. Furthermore, by linking the terms that identify the different abnormalities to psychiatric diagnoses in use at the time, e.g., “tangential thinking,” characterized by talking past and around the point, with the “schizophrenia”; “circumstantial thinking,” characterized by overbearing elaboration on insignificant details without losing track, with the “dementias”; and “rumination,” characterized by endless repetition of unpleasant thoughts, with “depressions,” the Heidelberg group set the foundation of a language for psychiatry and, within a period of less than two decades, turned psychiatry into a discipline with the capability to detect mental disease, and to separate reliably one mental illness from another.

Between 1913, when Jaspers’ General Psychopathology was first published, and 1959, when it’s seventh’ and last edition was published, “psychopathology” became the foundation of a "self-contained psychiatry," which qualifies for a distinct clinical discipline by providing a terminology in which pathologic mental events and mental illness can be expressed within the frame of reference of their own -- without the need to use the  terminology  of  another  discipline,  e.g., social behavior -- and can be shared across cultures and languages. By the time Kurt Schneider took the torch in 1946 at the Heidelberg clinic, "psychopathology" provided the necessary knowledge base to allow the teaching of psychiatry as a medical discipline. It also provided the necessary terminology for psychiatrists to meaningfully communicate with each other.

Introduction during the 1950s of the first set of psychotropic drugs with demonstrable efficacy in one or another psychiatric diagnosis raised hopes that “psychopathology,” and especially “phenomenology,” could provide the  necessary orientation  points for the discriminate use of psychotropic drugs and for the identification of pharmacologically sufficiently homogeneous populations that would allow the exploration of the biology of mental pathology by studying the action mechanism responsible for the therapeutic effects. There were hopes for a psychopharmacological re-evaluation of diagnostic concepts in psychiatry, but by the end of the 1960s it was recognized that psychiatry was moving in a different direction. 

Psychopathology and neuropsychopharmacology  

The dream of Moreau de Tours’ (1845) in the mid-19th century to use drugs in the study of insanity had become a realistic goal by the end of the 1950s with the introduction of effective pharmacological treatments, such as lithium, chlorpromazine, reserpine, imipramine, and iproniazid in psychiatry; the demonstration of the presence of monoamine neurotransmitters in the brain, such as norepinephrine and serotonin; the recognition of chemical mediation at the site of the synapse; and the construction of the spectrophotofluorimeter (Bowman,Caulfield and Udenfriend 1955). The capability to measure drug-induced changes in the concentration of neurotransmitter monoamines and their metabolites in the brain led to the development of neuropharmacology, a branch of pharmacology that deals with the detection of the mode of action of centrally acting drugs. It also opened the path for the development of neuropsychopharmacology, a new discipline that studies the relationship between neuronal and mental events with the employment of centrally acting drugs. By the end of 1955, the year the new technology (spectrophotofluorometry) became available, Pletscher, Shore and Brodie at the National Heart Institute in the United States, reported a decrease in brain serotonin levels after the administration of reserpine, a substance that was seen to induce depression in some patients when used in the treatment of hypertension. And, one year later in 1956, Pletscher first, and then Besendorf and Pletscher, reported an increase in brain serotonin levels after the administration of iproniazid, a monamine oxidase inhibitor that was reported to induce euphoria in some tubercular patients in the course of treatment (Flaherty 1952). 

One of the first to recognize that neuropsychopharmacology opened a new perspective in the understanding and treatment of psychiatric illness was Abraham Wikler, an American psychiatrist and pharmacologist. In his monograph on The Relation of Psychiatry to Pharmacology, published in 1957, he entertained the possibility that studying the mode of action of psychotropic drugs with known therapeutic effects might lead to the neurochemical underpinning of mental disorders, a prerequisite for the development of rational treatments.

Neuropsychopharmacology received wings in the 1960s from Arvid Carlsson’s (1962) report on selective changes on brain monoamines with psychotropic drugs. His findings set the stage for a development that led to the formulation of the catecholamine hypothesis of affective disorders by Joseph Schildkraut and William Bunney, and John Davis independently, in 1965, and the dopamine hypothesis of schizophrenia by Jacques Van Rossum, in 1967.

Yet, there were warning signals already showing in the early years that something was wrong. It was apparent to all those working with patients from the very beginning that one of the essential prerequisites of neuropsychopharmacological research, a clearly identified treatment responsive population, was not fulfilled. The heterogeneity in pharmacological responsiveness to the new drugs was so great within the diagnostic groups that it took eight years (1952-60) to demonstrate the therapeutic efficacy of chlorpromazine in schizophrenia, an obviously effective treatment for some patients, and seven years to demonstrate the therapeutic efficacy of imipramine in depression (Ban 1969; Casey et al 1960; Klerman and Cole 1965). 

To open the path for research in neuropsychopharmacology and the biology of mental illness, there was a need for a pharmacological re-evaluation of diagnostic concepts with the employment of psychopathology and psychiatric nosology, but this did not happen. Instead, to overcome the difficulties created by the heterogeneity within the diagnostic groups for the demonstration of therapeutic efficacy in a rapidly growing number of new psychotropic drugs -- a regulatory requirement by then for introducing a drug for clinical use in some countries -- a statistical methodology, the randomized clinical trial (RCT) was adopted in the late 1950s. There were unrealistic expectations that the data collected in RCTs would help to resolve the heterogeneity within the diagnoses by identifying treatment responsive populations with the use of linear regression equations or other statistical methods (Roth and Barnes 1981). But this was not to be the case. To meet the needs of RCTs for reliable diagnostic end-points, consensus-based diagnoses, such as the DSM-III (American Psychiatric Association 1980), and for the detection and documentation of changes, sensitized rating scales were adopted (Guy 1976). Since consensus-based diagnoses cover up their component diagnoses and rating scales are sensitized by retaining only the most sensitive symptoms and signs to treatment, their use has precluded the possibility of studying “psychopathology” and indices relevant to “psychiatric nosology” to find relevant information about the treatment responsive subpopulations within the diagnostic groups. 

During the 1960s and ‘70s, there were unrealistic expectations that the pharmacological heterogeneity within the diagnostic groups would be resolved by the replacement of old psychopathology-based diagnoses with diagnoses built from new buildings blocks based on biological measures, such as neuroendocrine tests, biochemical changes, neurophysiological indicators and/or brain images.  It was only in the 1980s, after the introduction of DSM-III, that it became evident that this was not to be the case.

With the replacement of nosology-based diagnoses by consensus-based diagnoses and psychopathological symptoms by rating scale scores, by 1987, the time of the postulation of a “clinical prerequisite” for rendering findings in neuropsychopharmacological and biological research in psychiatry interpretable, psychopathology (and especially phenomenological psychopathology) and psychiatric nosology became forgotten languages in psychiatry (Ban 1987, 2013).

INHN Education was launched with Carlos Morra and Ernst Franzek’s series in which one of the forgotten languages, “psychopathology,” will be rendered accessible to those interested in pursuing research in neuropsychopharmacology and in the biology of mental illness by defining a wide variety of psychopathological symptoms. A special feature of the series is the information relevant to the exploration of each symptom defined to establish its presence.

References:

American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. Third Edition. (DSM – III). Washington: American Psychiatric Association; 1980.

 

Ban TA. Psychopharmacology.  Baltimore: Williams & Wilkins; 1969.

 

Ban TA. Prolegomenon to the clinical prerequisite: psychopharmacology and the classification of mental disorders. Progress in Neuro-Psychopharmacology and Biological Psychiatry 1987; 1: 527 - 80.

 

Ban TA. The Forgotten Language of Psychiatry. (E-Book) Risskov: INHN; 2013

 

Ban TA. Psychopathology – unedited notes. INHN. Archives. July 14, 2016.

 

Besendorf H, Pletscher A. Beeinflüssung zentraler Wirkungen mit Reserpin und 5-Hydroxytryptamin durch isonicotinesauerehydrazide.  Helv Physol Acta 1956; 14: 383-90.  

 

Bowman RL, Caulfield PA, Udenfriend S. Spectrophotometric assay in the visible and ultraviolet. Science 1955; 122:  32-3.

Bunney WE, Davis JM. Norepinephrine in depressive reaction. Arch Gen Psychiatry 1965; 3: 483-94.

 

Carlsson A. Brain monoamines and psychotropic drugs. In: Rothlin E, editor.. Neuropsychopharmacology. Amsterdam: Elsevier; 1961.

 

Casey JF, Lasky JJ, Klett CJ, Hollister LE. Treatment of schizophrenic reactions with phenothiazine derivatives. Am J Psychiatry 1960; 117: 95-105.

 

Esquirol JED. Des maladies mentales.  Considerees sous les raports medical, hygienique et medico-legal. Paris: JP Bailliere; 1838.

 

Feuchtersleben E. Lehrbuch der Ärztlichen Seelenkunde. Vienna: Carl Gerold; 1845.

 

Flaherty JA. The psychiatric use of isonicotinic acid hydrazide: a case report, Delaware med J 1952; 24: 298-300.

 

Garrison FH. An Introduction to the History of Medicine. Philadelphia/London: WB Saunders; 1929.

 

Griesinger W. Die Pathologie und Therapie der PsychischenKrankheiten. Braunschweig: Wreden; 1845.

 

Guy W. ECDEU Assessment Manual for Psychopharmacology. Revised. Washington: US Department of Health, Education and Welfare. DHEW Publication No. (ADM)76-338; 1976. 

 

Jaspers K. Eifersuchtswahn: Entwicklung einer Persoenlichkeit oder Prozess. Zeitschrift für die gesamte Neurologie und Psychiatrie 1910; 1: 567-637.

 

Jaspers K. Allgemeine Psychopathologie. Berlin/Heidelberg: Springer; 1913.

 

Jaspers K. General Psychopathology. (Translated from the 7th edition of the German original into English by Hoenig J and Hamilton MW).  Manchester: Manchester University Press; 1962.  

 

Klerman GJ, Cole JO.  Clinical pharmacology of imipramine and related compounds. Pharmacol Rev 1965; 17:  101-41. 

 

Moreau de Tours J. Du Hachich et de L’Aliénation Mentale. Etudes Psychologiques, Paris:  Fortin & Mason; 1845.

Pletscher A.  Beeinflüssung des 5-Hydroxytryptamin stoffwechsels im Gehirn durch

Isonicotinsäurehydrazide.  Experientia 1956; 12: 479-80. 

Pletscher A, Shore PA, Brodie BB. Serotonin release as possible mechanism of reserpine action, Science 1955; 122: 374-5.

 

Roth M, Barnes TRE. The classification of affective disorders: a synthesis of old and new concepts. Compr Psychiatry 1981; 22: 54-77.

 

Schildkraut JJ. The catecholamine hypothesis of affective disorders. A review of supporting evidence. Am J Psychiatry 1965; 122: 509-22.  

 

Schneider K. Die Schichtung des emitionalen Lebens und der Aufbau der Depressions zustände. Z Ges Neurol Psychiat 1920; 59: 81-5.

 

Shorter E. A Historical Dictionary in Psychiatry. Oxford/New York: Oxford University Press; 2005.

 

Van Rossum JM, The significance of dopamine-receptor blockade for the action of neuroleptic drugs. In: Brill H,  Cole JO, Deniker P,  Hippius H,  Bradley PB, editors. Neuropsychopharmacology. Proceedings of the Fifth International Congress of the Collegium Internationale Neuro-Psychopharmacologicum (March 1966). Amsterdam:  Excerpta Medica Foundation; 1967, pp. 321-9.

Wernicke C. Lehrbuch der Geisteskrankheiten für Aerzte und Studierende. Vol. 2. Berlin: Theodor Fischer Kassel; 1881 – 1883, pp.  229-42.

 

Wikler A. The Relation of Psychiatry to Pharmacology. Baltimore: Williams & Wilkins;

1957.

Thomas A. Ban

September 29, 2016