Early : A New Clinical Entity

JMAJ 44(4): 182–188, 2001

Nobuo NAKAYASU

Associate Professor, Department of , Graduate School of Medicine, University of Tokyo

Abstract: Early schizophrenia as discussed in this paper is defined as “the early phase of a first-time Schub (acute exacerbation)” based on the definition of schizo- phrenia as “a chronic brain characterized by repetition of a specific Schub developing from the early phase to the full-blown phase and then to the sequela phase”. In the past, this stage was called the prodromal phase because only non- specific symptoms were generally observed. By referring to several prior refer- ences, the author re-discovered that symptoms specific to schizophrenia, although subtle, are latent in this stage. Considering the factors that the patient in this phase has an insight into his/her disease, typical antipsychotic agents such as chlor- promazine and haloperidol are not always effective, and patients often remain at this phase for several years, and hoping to increase early detection and early treat- ment of schizophrenia, the author proposed to describe this phase as early schizo- phrenia, a new clinical entity, in 1990. This paper re-iterates the concept of early schizophrenia and discusses the gender ratio, the age at onset, the clinical picture (diagnosis) and the treatment based on the author’s clinical experience of more than 10 years. Key words: Early schizophrenia; Schizophrenia; Prodrome; Early diagnosis; Early treatment

Introduction of early cancer and advanced cancer. As the concept of early cancer prompted early dis- The early stage of schizophrenia is, in quite covery and early treatment of cancer, the general terms, referred to as early schizophre- main purpose of the author’s proposed con- nia, but this paper discusses “early schizophre- cept of early schizophrenia is to contribute to nia” proposed as a new clinical entity by the early discovery and early treatment of schizo- author based on the new definition in 1990.4–10) phrenia. The concept, the gender ratio, the age The relation between early schizophrenia and at onset, the clinical picture, and the treatment ordinary schizophrenia may be likened to that are discussed below.

This article is a revised English version of a paper originally published in the Journal of the Japan Medical Association (Vol. 122, No. 13, 1999, pages 1995–2000). The Japanese text is a transcript of a lecture originally aired on May 2, 1999, by the Nihon Shortwave Broadcasting Co., Ltd., in its regular program “Special Course in Medicine”.

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Symptoms appearanee

Early Full-blown Sequela phase phase phase

ቢ Early symptoms Autochthonous experiences; heightened awareness; a vague sense of being watched; tense and perplexed mood ባ Full-blown symptoms Auditory ; delusional perception; ego disturbance; catatonic syndrome ቤ Sequela symptoms Blunted effect; hypobulia; loosening of association

Fig. 1 Schematic representation of the progression and course of schizophrenic Schub and early schizophrenia Left: The horizontal baseline indicates the state before each episode (or before the onset in the case of the first episode). The area above the baseline indicates the appearance of positive symptoms and that below the baseline the appearance of negative symptoms. Right: The progression of schizophrenia is understood as continuation of individual episodes, and the baseline descends as the number of episodes increases. Early symptoms appear in each episode, but only the early phase of the first episode (gray area) is called early schizophrenia.

Concept symptoms. As the author repeated careful examina- The definition of early schizophrenia4) is tions by referring to several prior studies,1–3) it based on the definition of schizophrenia was noted that symptoms specific to, albeit (excluding hebephrenic schizophrenia) of “a subtle, schizophrenia were latent in the chronic brain disease characterized by repeti- patient in this stage. In the beginning, there tion of a specific Schub, developing from the were observed four major symptoms or ten early phase to the full-blown phase, and then minor symptoms, which were described as to the sequela phase” and reads as “a clinical “four major symptoms specific to early schizo- entity meaning the early phase of a first-time phrenia”,4, 6) and followed by observation of 30 schizophrenic Schub and requiring a different specific and non-specific symptoms of early treatment strategy than that for ordinary schizophrenia.9) They will be discussed in fur- schizophrenia” (Fig. 1). It is pointed out, ther detail in the section of clinical picture. however, that this “early phase of a first- The author has four reasons for treating time Schub” means the stage, which used early schizophrenia as a clinical entity differ- to be referred to as “the prodromal stage” ent from ordinary schizophrenia; (1) symp- prior to the onset. Generally, this stage used toms specific to this phase are present, (2) to be described as presenting symptoms non- patients in this phase have insight into or specific to schizophrenia such as unidentified awareness of the disease unlike patients in the mental and physical complaints and neurotic full-blown phase, (3) typical dopamine recep-

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20

18

16

14

12

10

8

Number of patients 6

4

2

0 Early 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 childhood Age (90סFig. 2 Age at onset of early schizophrenia (n Blank bars indicate the times at onset described vaguely (from left to right) as “in primary school”, “in middle school”, and “in high school” as the median age of each period.

which was 3 to 4 ,4.5עtor blocking anti-psychotic agents such as examination was 18.9 chlorpromazine or haloperidol, which are years after the onset. This may be because effective for the full-blown phase, are not symptoms are so subtle that both the patient effective, suggesting that dopamine receptor and the family do not realize that they are blockers are not involved in its pathophysiol- caused by the disease. ogy, and (4) patients often remain at this phase for an extended period of time without Clinical Picture progressing to the full-blown phase (indicating the presence of a defense mechanism against As discussed above, there are as many as 30 progression to the full-blown phase.) symptoms observed in early schizophrenic patients if the specificity to schizophrenia is Gender and Age at Onset not questioned. In 102 cases examined by the author and his colleagues, prevalence of these As for the gender and the age at onset, both symptoms of early schizophrenia was studied the author and his colleagues observed that and 10 symptoms were frequently observed in the ratio was 1:1 for males and females as in more than 1/3 cases (33% or more), and these ordinary schizophrenia, and the age distribu- were classified into four higher rank groups tion at onset had two peaks, early childhood (Table 1, Fig. 3).9) It is almost impossible to and 14–15 (Fig. 2).10) check the presence/absence of 30 symptoms Four-fifth of 90 cases were distributed in in a clinical setting, but it becomes compara- puberty, and the mean age among 73 patients tively easy if the symptoms are limited to 10 that are most frequently observed. They are .3.9עthat they personally examined was 15.0 In one-fifth, some early symptoms had already considered useful for diagnosis because of appeared in early childhood, but exacerbation their high frequency. These 10 frequently seen occurred in puberty. The mean age at which symptoms of early schizophrenia are briefly exacerbation occurred in these 17 cases was discussed. coinciding with that of the age at 1) Autochonous thinking is thoughts that ,3.2ע15.6 onset in puberty cases. The mean age at first come spontaneously to mind. For instance, a

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Table 1 Highly Frequently Observed Symptoms of Early Schizophrenia Useful for Diagnosis

1. Autochthonous experiences ¥ Autochthonous thinking ¥ Autochthonous recollection ¥ Autochthonous fantasy images ¥ Autochthonous music images (musical ) 2. Heightened awareness ¥ Heightened auditory awareness 3. Tense and perplexed mood and its related symptoms ¥ Tense and perplexed mood ¥ A vague sense of being watched and/or “Leibhaftige Bewu§theit” ¥ Suspicion of being observed and commented on by the people around 4. Disorders of immediate cognition ¥ Disorders of immediate understanding and judgment ¥ Disorders of immediate memory

0 102030405060708090100% Autochthonous recollection 77.5 Suspicion of being observed and commented on by the people around 56.9 Autochthonous thinking 49.0 Autochthonous music images (musical hallucinations) 47.1 Heightened auditory awareness 46.1 Disorders of immediate understanding and judgment 43.1 Autochthonous fantasy images 42.2 A vague sense of being watched and/or ‘Leibhaftige Bewußtheit’ 39.2 Tense and perplexed mood 38.2 Disorders of immediate memory 35.3 Autochthonous inner speech and/or thought hearing 30.4 Heightened visual awareness 27.5 Anhedonia 27.5 Derealization 27.5 Elementary auditory hallucinations 26.5 Autochthonous visual images 21.6 Heightened vividness and sensory distortion of visual stimuli 18.6 Cenesthopathy 18.6

Formal visual hallucinations and/or conversational auditory 16.7 hallucinations that are judged as being unreal by the patient Heightened vividness and sensory distortion of auditory stimuli 15.7 Depersonalization 15.7 Paresthesias 13.7 Elementary visual hallucinations 12.7 Hallucinatory voices of calling one’s name 12.7 Changes of gustatory or olfactory vividness 10.8 Out-of-body experiences 9.8 Double mind and/or double body 9.8 A sense of swaying or floating of one’s body 9.8 Blank experiences 7.8 Heightened proprioceptive awareness 2.9

(102סFig. 3 Incidence of (30) symptoms of early schizophrenia (n

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patient complains that “thoughts that are irrel- the sound of an electric train running nearby”. evant to what I am consciously thinking come A person becomes unintentionally aware of to me in surges”. Rambling and incoherent auditory stimulus of a slight sound or a human thoughts come to the mind in succession. voice that suddenly and unexpectedly comes 2) Autochthonous recollection is experi- into his surroundings, and his attention is enced when “scenes of by-gone days come to diverted by the sound. This is often accompa- mind frequently. They are usually scenes of nied by astonishment. Although the incidence myself playing with friends, clear and colorful of such phenomenon did not exceed 1/3 of as in the actual setting, and people move and the total, there are symptoms such as height- the scene changes. I do not think I hear voices, ened visual awareness and heightened pro- but I feel as if I am conversing with someone” prioceptive awareness that fall in the same according to a patient. Emotional scenes that category. This symptom should therefore be the patient experienced in the past spontane- classified under the higher rank concept ously come back to him without relevance to of “heightened awareness”. the current situation or mood, and he can “see 6) Tense and perplexed mood is described it inside his head or hear the sound actually”. as “suppose I am up on stage. Before that, you 3) Autochthonous fantasy images are get tense. I continually have that kind of feel- explained by a patient as follows. “The name ing.” While the patient is tense because he of someone I like comes to mind and I feel anticipates some incident, he is perplexed that the person is actually with me and I talk because he does not know what he is antici- to that person. I am half aware that they are pating. This mood consist of autochthonous fantasies, but half the time I am totally tenseness and perplexion. immersed in that scene in the other half. When 7) A vague sense of being watched and/ I come to myself, I find me sitting in front of or “Leibhaftige Bewußtheit”. For instance, a the desk.” This is generally described as day- patient says “I am studying at night in my dreaming, and consists of visual and auditory room and have the feeling that I’m being images of a fantasy scene unfolded like a watched from behind by a spirit. When I turn story. around, no one is there, but when I look for- 4) Autochthonous music images are ex- ward, I feel again that someone is still watch- plained as follows. “I feel like I am giving a ing me.” The sense of being watched is clear concert in my mind. Commercial songs and and certain, but the patient knows that there popular songs that I half know come and go in is actually nobody looking at him. As for this quick succession.” The expression “autochtho- “watcher”, there are various types ranging nous music images” is used to indicate that from vague and unclear (vague sense of being this is also an autochthonous experience, but watched) to clear perception of the presence it may be described as musical hallucination. (Leibhaftige Bewußtheit). Autochthonous thinking, autochthonous 8) Suspicion of being observed and com- recollection, autochthonous fantasy images, mented on by the people around. A patient and autochthonous music images as discussed says that “when I see people talking around above fall under a higher rank concept that me, I feel that they are watching me or com- is widely referred to as “autochthonous menting about me, even though I half know experiences”. that it is not so.” In a place with people 5) Heightened auditory awareness is an around, he feels that he is being watched or experience such as “I become highly agitated being commented on with malice. Different when I suddenly hear other people’s voices, from delusion of persecution, he thinks only sudden noises such as opening of the door or half of what he believes (or to be more pre-

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cisely, believes it now and denies it the next 30 moment). The above discussed three symptoms, i.e., 25 tense and perplexed mood, a vague sense of being watched and/or “Leibhaftige 20 Bewußtheit” and suspicion of being observed 15 and commented on by people around may be 27 summarized as a higher rank concept of “the Number of patients 10 22 tense and perplexed mood and its related 18 symptoms”. 5 9) Disorder of immediate understanding or 7 8 9 1 6 22 judgment. For instance, a patient feels that “it 0 is hard to understand what others are talking 012345678910 Number of symptoms or what is being said on television, and it is Fig. 4 Patient distribution for number of symptoms not possible to reconstruct the content in experienced of the symptoms (10) of early mind”, “I am impatient because I lack judg- schizophrenia, which were observed with high frequency or more than 1/3 ment. For instance, chopsticks are standing in a chopstick stand, . . . . and I cannot immedi- ately tell the differences”. He is no longer able to understand the daily conversation of other people, which he used to understand instantly, symptoms was 4.7. In other words, all patients or he cannot see the differences in shape or experienced approximately half of these color as in the case of chopsticks discussed symptoms (Fig. 4), demonstrating the author’s above. theory that confirming the presence of these 10) Disorder of immediate memory. A symptoms is useful for diagnosis. patient working as a temporary help in a sou- venir shop in an amusement park said, “I for- Treatment get what I was going to do. Because I forget all the time so that when I am asked to go to Lastly, treatment of early schizophrenia is the warehouse to fetch something, I always discussed briefly. The first concerns the atti- take a piece of the thing that I am supposed to tude of the treating physician. In order to fetch with me.” The patient experiences that respond to the patient’s tense and perplexed he cannot remember what he was going to do mood, the physician should be serious and or what he was told immediately before. This grave above anything else. disorder of immediate memory is not continu- The second concerns the techniques of ous as in the case of dementia, and is charac- interview. It is important to conduct a detailed terized by its random appearances. question and answer session in order to These two types of disorders, i.e., disorders describe the symptoms in an objective and lin- of immediate understanding and judgment guistic manner. In ordinary type schizophre- and disorders of immediate memory may be nia, questioning the details of hallucination summarized as a higher rank concept of “dis- and delusion is nearly always forbidden. But orders of immediate cognition”. this is contrary in the case of early schizophre- As discussed above, the 10 symptoms nia. Since the patient does not understand the are frequently observed in more than 1/3 experience he is undergoing and is extremely of early schizophrenia patients. According to uneasy and tense, asking detailed questions the author’s study of 102 cases,9) the mean of will cause the patient to view these experi-

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ences in an objective way and to recognize the inexplicable), and therefore many of such same as something different from his original patients are misdiagnosed as “school refusal”, character. In other words, putting distance “adolescence crisis”, “depressive state”, or between him and the symptoms is effective for “too nervous”. The author hopes that this treatment. paper would be of some use for daily clinical Thirdly, the author usually administers 100– scene. 300 mg/day of sulpride as a drug of the first choice. This drug alone improves about 1/2 to REFERENCES 2/3 of the patients. If this is not effective enough, the dose may be increased to 600 mg/ 1) Clérambault, G., de: Automatisme mental. day, or a small amount of fluphenazine (about Oeuvre psychiatrique, Tome II, pp.453–654, 0.75–1.5 mg/day) may be administered addi- PUF, Paris, 1942. tionally. (Anti-parkinsonism agent should 2) Gross, G., Huber, G., Klosterkötter, J. et al.: always be dosed concurrently in order to pre- BSABS. Bonner Skala für die Beurteilung vent extrapyramidal side effects.) It is, how- von Basissymptomen. Springer-Verlag, Ber- lin, 1987. ever, true that there are a considerable num- 3) McGhie, A. and Chapman, J.: Disorders of ber of cases which utterly fail to respond to attention and perception in early schizophre- this treatment regimen. nia. Br J Med Psychol 34: 103–116, 1961. Fourthly, it is essential to determine and tell 4) Nakayasu, N.: Early Schizophrenia. Seiwa the patient that he is suffering from a disease Shoten, Tokyo, 1990. (in Japanese) of the brain, for which he is not responsible. 5) Nakayasu, N.: Symptomatology of Schizo- Almost all the patients are relieved to hear phrenia—From descriptive phenomenology this. A patient related later “I wouldn’t have to neuropsychological understanding. Seiwa Shoten, Tokyo, 1991. (in Japanese) known what to do if I was told that I was not 6) Nakayasu, N.: Early schizophrenia. Asian ill”. As for the name of the disease, telling the Med J 38: 488–495, 1995. patient that he is suffering from early schizo- 7) Nakayasu, N.: Early Schizophrenia: Addi- phrenia may even in this day drive him to tional papers. Seiwa Shoten, Tokyo, 1996. suicide. Therefore, the author usually tells that (in Japanese) the patient is suffering from “oversensitive 8) Nakayasu, N.: Symptomatology of early schiz- disorder”, a name that may be false. However, ophrenia in Japan. Proceeding of the 6th this naming seems to be adequate to describe Cultural Psychiatry Symposium in Japan, the experiences or symptoms of the patient Korea and Taiwan—Symptomatology of Schizophrenia in East Asia. pp.1–23, The and appears to be acceptable. At any rate, the East Asian Academy of Cultural Psychiatry, important thing is the physician’s recognition 1996. that the patient is suffering from a disease, 9) Nakayasu, N., Harima, H. and Seki, Y.: Early irrespective of the name. symptoms. Ed. Matsushita, M.: Clinical Psy- chiatry Lecture 2. Schizophrenia I. pp.313– 348, Nakayama Shoten, Tokyo, 1999. (in Conclusion Japanese) The clinical picture of “early schizophre- 10) Nakayasu, N., Seki, Y. and Harima, H.: Age at onset and prevalence of symptoms in early nia”, a clinical entity proposed by the author, schizophrenia, and outcome of treatment— was discussed. The author would like to con- Seeking for pointers in early discovery and clude that only a limited number of patients early treatment of schizophrenia. Psychiatria can positively describe the details of their et Neurologia Japanonica 101: 898–907, 1999. abnormal experiences (they appear to be truly (in Japanese)

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