Thomas A. Ban
Neuropsychopharmacology in Historical Perspective
Psychopharmacology and the Classification of Functional Psychoses
Neuropsychopharmacology in Historical Perspective
6. One- and Two-Dimensional Diagnoses
Diagnoses of functional psychoses are based on descriptive characteristics. Originally, these characteristics were restricted to cross-sectional psychopathology, but by the end of the 19th century they included characteristics of the course (two-dimensional) and the final stage of the illness (three-dimensional), referred to as outcome or end-state.
The perspective of supplementing descriptive-psychopathological symptoms with biological measures opened unforeseen possibilities. Introduction of paper, liquid and gas chromatography, mass spectrometry and radio-immuno-assay, rendered measurement of biochemical changes in the CNS accessible to laboratory investigations. Supplementing traditiona1 electroencephalography with nuclear magnetic resonance measures, X-ray transmission tomography and positron emission tomography rendered the examination of specific brain sites possible (Buchsbaum, Ingvar, Kessler et al. 1982; Gur 1985; Hendrie 1985; Mathew 1985; Nasrallah and Coffman 1985).Yet, the meaningfulness of findings with these sophisticated measures was dependent on whether they could be linked to a pharmacologically homogeneous patient group.
In the following the conceptual deve1opment of classification(s) relevant to functional psychoses will be outlined.
One-Dimensional Diagnosis: Concept of Psychosis
In spite of its extensive use, there is no generally accepted definition for the term "psychosis." In everyday psychiatric parlance it refers to mental illness of sufficient severity to produce conspicuously disordered behavior with lack of insight. The behavior of “psychotic” patients cannot be understood as an extension or exaggeration of ordinary experiences (Leigh, Pare and Marks 1972).
Jaspers (1913a, 1959, 1963) used the term “psychosis” in reference to diseases which "seize upon the individual as a whole,” whereas in the United States the term was employed primarily in reference to patients with hallucinatory experiences, delusional thinking and/or catatonic symptoms.
An important contribution to the development of the term was made by Schneider (1959). He contended that the term “psychosis” should be used only to designate psychopathological manifestations which are the consequence of a disease process. His concept of “psychosis” corresponds with Jaspers' (1963) notion that psychoses are “disease processes, regardless whether they are hereditary disorders beginning at certain times of life or called into being by exogenous lesions.”
The concept of psychosis put forward by Jaspers and Schneider was operationalized by Fish (1974). In Fish's definition the characteristic features of “psychosis” include lack of insight, distortion of the whole personality (by the illness), construction of a false environment (out of subjective experiences), gross disorder of basic drives (including that of self-preservation) and inability to make a reasonable social adjustment (Hamilton 1974). In the KDK Budapest (Pethö, Ban, Kelemen et al. 1984), psychosis is defined as a non-specific syndrome characterized by lack of “insight” and psychopathological symptoms of sufficient severity to disrupt everyday functioning. The collapse of customary ways of social life may lead to hospitalization.
Distinctly different from “psychoses” are “psychic deviations which do not wholly involve the individual” (Jaspers 1963). They include patients whose personality is only in part affected, who can distinguish between their subjective experiences and reality and who do not construct a false environment (Hamilton 1976). In diagnostic terms, “psychic deviations” include “personality disorders,” i.e., variations of human existence which differ from the norm quantitatively rather than qualitatively, and “neuroses, i.e., reactions of abnormal personalities to moderate or mild stress and reactions of normal personalities to severe stress (Schneider 1959).
“Psychosis” without any qualification is a diagnosis only within a one-dimensional model of classification, i.e., a classification which is based exclusively on cross-sectional assessment of psychopathology. Accepting “psychosis” as the endpoint yields a one-dimensional treatment modality with antipsychotic-neuroleptic drugs. The underlying assumption is that the different forms of illness are different stages of one and the same disease (psychosis) process (Neumann 1859) and consequently can be controlled by one and the same (or pharmacologically similar) medication.
Today (mid-1980s) there are at least 19 antipsychotic drugs available for the treatment of “psychosis” in the United States and about 12 more around the world. Structurally most of these drugs are secondary or tertiary amines containing at least one aromatic ring linked to an amine by an intermediate chain; and pharmacologically most of these drugs are active inhibitors of apomorphine-induced vomiting in dogs, amphetamine-induced stereotypic chewing and non-stereotypic agitation in rats and epinephrine- and NE-induced mortality in rats. They also inhibit intracranial self-stimulation and conditioned operant behavior in all laboratory animals. At somewhat higher doses, traditional neuroleptics induce cataleptic immobility with a reduction of spontaneous motility and indifference towards the environment. And at an even higher doses, they induce ptosis, ataxia, prostration and other signs of CNS depression (Janssen 1973).
The most consistent finding following chronic (l to 3 weeks) antipsychotic administration is a dopamine (DA)2 receptor blockade and a consequent increase in the number, with a decrease in the affinity, of these receptors in the striatum and mesolimbic areas (Burt, Creese and Snyder 1977; Muller and Seeman 1977, 1978; Theodorou, Gommeren, Chow et al. 1981). Therefore, one may hypothesize that the biochemical substrate of psychosis is in the DA structures of the limbic lobe. At variance with this contention, are findings in clinical psychopharmacological studies which suggest that there is a differential therapeutic response in psychotic patients to antipsychotic drugs. Although antipsychotics undoubtedly are the most effective treatment for psychoses, some psychotic patients remain refractory to antipsychotic drugs and require other treatment modalities for control. Since a differential therapeutic response indicates biological heterogeneity, the findings of a differential therapeutic response are in line with the contention that psychosis consists of more than one diagnostic groups.
Organic vs Functional
Conceptual separation of “organic” from “functional” psychoses represents the first meaningful dichotomy within psychiatry. The adjective “organic” implies that the psychosis is intrinsically linked, if not exclusively the result of systemic, including neurological disease. On the other hand, the adjective “functional” implies that the psychosis is a result of a sui generis psychiatric illness in which there is a primary dysfunction in the operation and performance of the brain. This is in accordance with other branches of medicine in which a “functional disorder” refers also to a primary dysfunction with an unidentified structural change. As the concept of “functional psychosis” assumes a structural change, Schneider's (1959) “somatogenic postulate” is based on the belief that “functional psychoses are always of somatic origin” even if the cause is not known and/or the morphological substrate has not been identified (Pichot 1983).
Conceptual separation of organic from functional psychoses was a significant step in the development of psychiatry. It opened the possibility to identify cross-sectional psychopathological syndromes which indicate organicity with a high level of probability. This in turn yielded etiology-based diagnoses and causal treatment in some of the organically determined psychoses.
With the decrease in the prevalence of “organic psychoses” in the adult psychiatric population, by the virtual elimination of “general paralysis of the insane (GPI), a form of cerebral syphilis” which once constituted 10% of all hospitalized psychiatric patients, there has been a shift in the proportion of patients in adult psychiatry from the organic to the functional psychoses during the 1950s and 1960s.
The shift in the proportion of patients from “organic” to “functional” was followed by a shift in the site of psychiatric care from hospital to community. It was this shift, coupled with the emergence of “psychodynamic psychiatry,” that focused attention on “anxiety disorders.” Introduction of propanediols (meprobamate) first and, subsequently, benzodiazepines (chlordiazepoxide), rendered anxiety disorders accessible to biological research (Berger 1954, 1957, 1964; Sternbach 1972; Tobin and Lewis 1960).
Acute Exogenous Predilectional Types
Separation of organic from functional psychoses provided the necessary orientation points for Karl Bonhoeffer (1909) to develop his concept of “acute exogenous psychoses,” i.e., psychoses associated with and/or the result of systemic disease. Within Bonhoeffer's frame of reference “exogenous psychoses” are non-specific secondary manifestations of systemic disease and as such distinct from sui generis psychiatric disorders.
Bonhoeffer's concept of “exogenous predilectional types” is based on the recognition that psychotic reactions associated with systemic disease appear in one of four forms:
1. delirium which may occasionally be disguised by hallucinosis as the dominant clinical feature;
2. epileptiform reactions which may present as states of anxious or frenzied motor excitement, or alternatively as quiet, affectless twilight states;
3. stupor; and
4. confusional states which may show hallucinatory, catatonic, or dissociative features.
Since similar reactions may occur in association with different illnesses and the course of illness is not determined by the presenting clinical picture, Bonhoeffer maintained that the prevailing psychopathological syndrome reflects a specific predisposition which does not provide interpretable clues for an etiological understanding of the disease.
Bonhoeffer's concept of “acute exogenous psychoses” is subsumed under the heading of “symptomatic psychoses” in the British literature. The typical obligatory feature of these psychoses is disturbance of consciousness that may become manifest in altered states of consciousness, e.g., delirium that may accompany acute disease or in “lowered states of consciousness” which vary in degree from “daze” (Benommenheit), frequently experienced in the common cold, to “coma,” i.e., loss of consciousness seen in enteric fever, septicemia.
In the psychoses caused by subacute and chronic illness, consciousness is less clouded or may even be clear. This condition has been differentiated from delirium and referred to “confusional state.” It is also referred to as “amentia” in German psychiatry and as “subacute delirious state” in British psychiatry (Mayer-Gross, Slater and Roth 1960). Other, atypical-facultative manifestations of exogenous psychoses are dependent on a general or a specific predisposition. The development of a transient catatonic, hyperthymic, dysthymic or amnestic syndrome is attributed to a general predisposition, while the development of a transient schizophreniform, paranoid or hallucinatory reaction to a special predisposition. The resultant “atypical forms” with full recovery (reversibility) are referred to as “transient organic syndromes” (Durchgangsyndrome) by Wieck (1956, 1957).
All these different typical and atypical forms of disease may terminate in full recovery or yield to 1. organic neurasthenia, also referred to as irritable debility or emotional hyperesthesia, 2. Korsakoff’s amnestic syndrome or 3. generalized dementia (Nyiro 1962). Organic neurasthenia provides the link between acute exogenous (symptomatic) psychoses with prevailing delirium and the subacute and the chronic exogenous (organic) psychoses with prevailing dysmnesia and/or dementia (Table 1).
Area of Psychopathology
1. Disorders of Consciousness
2. Disturbances of Orientation
3. Disorders of Memory
The area of psychopathology (+) prevailingly affected in acute, subacute and chronic organic psychoses.
Delirium, Dysmnesia and Dementia
Recognition that the continuous presence of traumatic biological factors may result in dementia threw light on Bayle’s (1822, 1825, 1826) thesis that persistence of “arachnitis” (during the third and final stage in the development of general paralysis) yields to dementia in patients. It also brought to attention some of the early contributions of Pinel (1801). In his classification of psychiatric disorders, he was the first to employ the term “dementia” to describe illnesses which lead to intellectual deterioration. The conclusive distinction between “inborn idiocy” and “acquired dementia” was made by Esquirol (1838) almost 40 years later.
It was the early 19th century French school of psychiatry which had delineated the essential psychopathological features that result from persistent (chronic) brain damage. However, the findings of the French school became meaningfully interpretable only after the determination that “delirium” is the essential psychopathological features of acute biological trauma by the early 20th century German school.
Integration of the contributions of the two schools yields the still prevalent position that delirium, dysmnesia and dementia indicate the presence of somatic factors in the etiology of psychotic disease with a high level of probability. The three “Ds” provide the necessary clues for the separation of organic psychoses with psychopathological manifestations prevailingly in the connecting function, such as consciousness, memory and personality, from the functional psychoses with psychopathological manifestations prevailingly in the perceptual cognitive, relational-affective and motor-adaptive functions, such as perception, thoughts, emotions, mood and motor behavior. Identification of the differential psychopathological features involved in organic and functional psychopathologies and recognition of the relationship between brain structures and the sites of psychopathology has raised considerations that in case of non-specific organic psychopathology the primary impairment responsible for the psychopathological changes might be in the reticular formation and temporal lobe structures intrinsically linked with connecting functions, whereas, in case of specific functional psychopathology the primary impairment responsible for the psychopathological changes might be in limbic lobe structures in general and in frontal, parietal, temporal and/or occipital structures in particular, intrinsically linked with relational affective, motor-adaptive and perceptual-cognitive functioning.
Differentiation between functional and organic (exogenous) psychosis cannot be made within a one-dimensional model of classification. It can be made only within a two-dimensional model because cross-sectional psychopathological symptom profiles do not suffice. They need to be supplemented with information on the form of onset and antecedent etiological event(s), (biologic factors) such as somatic illness or brain disease, for the interpretation of findings. The presence of somatic illness (including brain disease) immediately prior to or at the onset of psychosis, however, does not exclude the possibility that the psychosis is functional in nature. The same applies when the somatic illness and the mental disturbance do not run a parallel course (Pethö, Ban, Kelemen et al. 1984). Recognition of functional and organic psychoses divides the psychotic population into two major groups and only in one of these two populations, in functional psychosis, are antipsychotic drugs the primary treatment of choice. In the organic psychoses treatment should be directed against the etiology of the disease, e.g., nicotinic acid in case of pellagra, neurosurgery in case of brain tumor.
In patients with organic psychosis causal treatment may need to be supplemented transiently by the administration of an antipsychotic drug. The use of antipsychotics as primary treatment, within a two-dimensional model of psychiatric classification, is restricted to patients with functional psychosis (Table 2).
1. Connecting Functions
The area of psychopathology(+) prevailingly affected in organic and functional psychoses.
Functional Psychosis: Reactive vs Endogenous
There are two distinct populations in functional psychoses. One population is conventionally referred to as autochthonous, or endogenous, and the other as reactive, or psychogenic.
Psychic reactions arising from conflictua1 experiences and external events are exogenous, whereas phases and processes arising from inner causes without an external event are endogenous (Jaspers 1963). Within this frame of reference, the concept of endogenous psychosis, which has its origin in Morel's (1857, 1860) teachings, implies an innate genetic biological defect, while the concept of psychogenic or reactive psychosis implies the presence of a psychic trauma (Pichot 1983).
Psychogenic (Reactive) Psychosis
The diagnostic concept of psychogenic psychosis has evolved through the work of the Danish psychiatrists Wimmer (1916), Faergeman (1945, 1963), Strömgren (1968, 1974) and Retterstal (1978). In the integration of the concept with main-stream psychiatry, Jaspers’ (1913a,b) criteria of “pathological reaction” played an important role. According to Jaspers, to fulfill the criteria of pathological reaction there must be an adequate precipitating factor standing in a close time relationship with the reactive state. There must also be a meaningful connection between the content of the experience and those of the abnormal reaction, and the reaction must be reversible, i.e., the abnormality must disappear when the primary cause for the reaction is removed. In this respect pathological reactions contrast with morbid processes which appear spontaneously. Furthermore, Jaspers suggests that reactive states can be classified in at least three different ways, i.e., according to what precipitates the reaction, according to the particular psychic structure displayed in the reactive state and according to the type of psychic constitution that determines the type of reactivity
In his classic text August Wimmer (1916) defined psychogenic psychoses as “clinically independent psychoses” caused by “mental trauma” acting on a “predisposed foundation.” Furthermore, he suggested that its two essential components, i.e., predisposition and mental trauma, determine the “moment for the start of the psychosis, the fluctuations of the disease, and very often also its cessation.” He contended that “the form and the content of these psychoses were more or less directly and completely (comprehensibly) determined by the precipitating mental factors.” Psychogenic psychoses almost always end in full recovery. If this is not the case, the diagnosis may need to be reconsidered.
Important contributions to the understanding of “psychogenic psychosis” were made by Eric Strömgren (1968, 1974). For Strömgren, these psychoses are psychogenic in the sense that “the mental trauma must be of such a nature that the psychosis would not have arisen in its absence.” There must be a close temporal relationship between the onset of the psychosis and the traumatic experience. There is a relationship also between the traumatic situation and the course of the psychosis. This is to the extent that “if the situation ceases to exist the psychosis will usually stop immediately.” But even if the situation persists, according to Strömgren “the psychosis will not go on forever.”
Insofar as the “etiology” of psychogenic psychosis is concerned, Strömgren divided exogenous traumatic factors into five groups: experiences of an entirely impersonal character, social disasters, conflicts within the family, isolation and inner conflicts. He maintained, however, that “on the whole one cannot expect to find a clear correlation between the quality and the quantity of the trauma and the type or extent of the patient's reaction.” This implies that much depends on the special sensitivity, i.e., “catathymic predisposition” of the patient, which in turn suggests that endogenous factors possibly play a predisposing role. In favor of this contention are the relatively uniform genetic findings that patients with psychogenic psychosis have a high incidence of “mentally abnormal subjects” in their families.
Taking all these factors into consideration Pethö, Ban, Kelemen et al. (1984) suggest that in “psychogenic psychosis” the onset of psychopathology must be attributable beyond reasonable doubt to a precipitating life event and the “psychotic content” must be fully understandable with respect to the precipitating life event and/or on the basis of patient's life history. The psychosis must appear as an integral part of patient's life history and the intensity of the traumatic experience should sufficiently explain the emergence of the psychosis. There should be thematic continuity between the traumatic experience and the psychotic content; and there should be a meaning to the psychosis appropriate to the situation with manifestations such as theatricality and protest directed towards the onlookers. To prevent overlap between “reactive” and “endogenous” psychosis the absence of certain endogenous psychopathological symptoms, such as inhibited thinking, tangential thinking, flight of ideas, perseveration, neologisms, blunted affect and/or autistic behavior is a prerequisite for the diagnosis of psychogenic psychosis.
Today, psychogenic psychosis is recognized in many countries including Denmark, Norway (reactive psychosis: psychogenic and constitutional), France (psychoses reactionelles) and the USSR (reactive psychosis) (Giljarowski 1960; Widlocher 1958).
The diagnosis of endogenous and reactive psychogenic psychoses requires a two-dimensional model of diagnostic classification as cross-sectional psychopathological symptom profiles need to be supplemented with information on the form of onset and antecedent-etiologic event. Accepting endogenous and reactive psychoses as endpoints divides the functional psychotic population into two major groups and only in one of these two, in “endogenous psychosis,” is treatment with antipsychotic drugs the primary choice. In reactive psychosis, treatment with antipsychotics usually does not suffice and needs to be combined with other therapies.
Psychogenic (reactive) psychosis is a two-dimensional diagnosis. Accordingly, an essential prerequisite for this diagnosis is that the emergence of the cross-sectional psychopathological picture of the psychosis can be satisfactorily explained by the “intensity of traumatic experience.” Because the subject matter of the psychosis is organized around the traumatic experience, the content of the psychosis should be comprehensible. The third essential characteristic of psychogenic (reactive) psychosis is goal-directedness. It is through this goal-directedness that the psychosis becomes an integral part of patient's life history.
There is no consensus about the incidence of psychogenic psychosis. Strömgren (1968) estimates a morbidity risk (lifetime expectancy) of about l%. He found that 10% of all, and 15-20% of all newly admitted psychotic patients to the Aarhus Psychiatric Hospital in Risskov (Denmark), during the period from 1953 to 1968, belonged to the psychogenic group. On the other hand, Faergeman (1963) found that only about 2% of the patients admitted to the Psychiatric University Clinic at Copenhagen during the period from 1924 to 1926 were diagnosed as psychogenic psychosis.
On the basis of the clinical picture, Schneider (1927) separates psychogenic psychosis into three diagnostic groups: “emotional reactions” (approximately 65%), “disorders of consciousness” usually referred to as “dissociative-confusional states” (approximately 15%) and “paranoid states” (approximately 20%). Among the “emotional reactions,” depression is the most frequent. In typical cases it is characterized by a passive attitude and lack of interest in the surroundings. However, atypical cases may occur. Included among the atypical cases are paradoxical reactions such as “funeral manias” (Hollender and Goldin, 1978) and “emotional paralyses,” described by Baelz (1901).
Distinctly different from the emotional reactions are “dissociative confusional” states with prevailing “disorders of consciousness” which in typical cases are manifested in the form of delirious reactions or clouded states. Included among the clouded states is the Ganser syndrome (Ganser 1965) in which the flight from reality is goal directed.
The third group of psychogenic psychosis consists of “paranoid states.” Among them the most frequently encountered is a "”comprehensible paranoid reaction,” the “sensitive delusions of reference” described by Kretschmer (1927, 1966, 1984).
While retaining the three forms of psychogenic psychosis, Pethö, Ban, Kelemen et al. (1984) divided psychogenic psychosis into two major groups. One with an acute onset consists of three subtypes: psychogenic regressive psychosis, psychogenic affective psychosis and psychogenic paranoid psychosis. The other with a subacute onset, psychogenic delusional development, consists of four variants: passionate (idealists, conjugal paranoia, erotomania), litigious (querulous, reformatory zealotry), hypochondriacal (delusions of parasitosis, Shikano syndrome) and symbiotic (folie a deux, folie a trois). The psychogenic psychoses (regressive, affective and paranoid) yield to full remission with resolution of psychopathological symptoms usually within three months, but psychogenic delusional development has a tendency for chronicity and may result in transformation without disintegration of the personality. Prevailing characteristics of psychogenic regressive psychosis are clouding of consciousness and impaired orientation; of psychogenic affective psychosis, exaltation or depression; and of psychogenic paranoid psychosis, delusions of reference. In contrast to the acute forms, psychogenic delusional development is characterized by a logically derived systematized delusional system, which spreads within a restricted area. It is assumed that it develops to a “key experience” in patients with paranoid personality traits.
It is a commonly held view that the form of psychogenic psychosis depends on constitutional factors. “Syntonic” or “extrovert” patients respond with an “emotional reaction,” “hysterical” display, a “dissociative-confusional state,” and “schizoids” react with a “paranoid syndrome.” However, Strömgren (1958, 1968, 1974) maintains that more important than constitution is the nature of the traumatic experience. He suggests that emotional reactions are the result of simple situational conflicts; dissociative-confusional states are the outcome of a sudden disruption of the patient's image of his environment; and paranoid disorders are the consequence of a severe blow to one's “self-esteem” or to “one's self-image.”
The question whether the three syndromes described are distinct diagnostic entities - whether they are meaningful in terms of prognosis and/or treatment - cannot be answered within a two-dimensional model of psychiatric classification. By employing a three-dimensional model, however, it was noted that the duration of illness was significantly different for the three acute psychogenic syndromes. Dissociative-confusional states last only from a few hours to a few days; emotional reactions (e.g., depression) from a few days to a few weeks and paranoid reactions from a few weeks to a few months.
Corresponding with the diagnostic category of “psychogenic psychoses” is the diagnostic category of “other nonorganic psychoses” in the ICD-9. This category is restricted to a group of psychotic disorders largely or entirely attributable to a recent life experience. Included in this category are nonorganic psychoses depressive type (reactive depressive psychosis, psychogenic depressive psychosis); excitatory, reactive confusion (psychogenic confusion, psychogenic twilight state); psychogenic paranoid psychosis (protracted reactive paranoid psychosis); and other and unspecified reactive psychosis (hysterical psychosis, psychogenic psychosis, psychogenic stupor). Diagnoses corresponding to “psychogenic delusional development” are not limited to “psychogenic paranoid psychosis” in the ICD-9 but include “induced psychosis” (folie a deux, induced paranoid disorder) and other paranoid states (paranoia querulans and sensitiver beziehungswahn).
Closest to the category of “psychogenic psychoses” is the diagnosis of “brief reactive psychosis” in the DSM-III. However, the diagnosis of “brief reactive psychosis” does not correspond with any diagnosis within the “psychogenic psychoses.” The only correspondence between the two diagnostic systems relevant to psychogenic psychoses is the one between “psychogenic paranoid psychosis” and “acute paranoid disorder” of the DSM-III. Patients with “psychogenic delusional development” may be diagnosed as “shared paranoid disorder” or “paranoia” in the DSM-III.
In the treatment of psychogenic psychoses, antipsychotic drugs are extensively employed. Despite this, the fact remains that there is no convincing evidence, on the basis of properly designed and conducted clinical experiments, that they are therapeutically effective and/or superior to the benzodiazepines. Especially disappointing is the limited therapeutic responsiveness to antipsychotics in paranoid reactions. Apart from decreasing delusional dynamics, i.e., the force or intensity of the affective drive which accompanies the delusion, they have little effect on the content disorder of thinking (systematized delusions).
While psychogenic paranoid reactions seem to persist despite the administration of antipsychotics, psychogenic dissociative-confusional states promptly remit in the course of administration of the same drugs. In view of the usually short duration (natural course) and reported therapeutic responsiveness of these conditions to barbiturate-induced abreactions (Sargant and Slater 1963), it is difficult, in the absence of placebo-controlled experiments, to decide whether one is dealing with spontaneous remission or drug effects.
The situation is even more confounded in psychogenic emotional reactions. As treatment with antidepressants does not seem to have satisfactory therapeutic effects (Bielski and Friedel 1976) and antipsychotics may aggravate depression, as an ultimate resort not infrequently patients with psychogenic depressive (emotional) reactions are treated with electroconvulsive therapy.
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May 13, 2021