The onset of psychosomatic diseases in children has a close relationship to the developmental level of the central nervous system (Abb. CNS). For example, sleep terror disorders are seen in early childhood, tic disorders from early childhood to childhood, recurrent abdominal pain and headache in childhood and puberty and enuresis are needed for evaluation and treatment in childhood. The level of socialization also depends on the developmental levels of CNS. The relationship to family is very important, especially to mothers in infancy and in early childhood, conflicts with siblings from early childhood to childhood and the relationships with friends and teachers from childhood to puberty. Recurrent abdominal pain and headache are common as psychosomatic symptoms in the outpatient clinic of paediatrics. There were 231 patients with reccurent abdominal pain and/or headache in our clinic during the past 3 years. In 51 patients out of 231,these symptoms were recognized as psychosomatic ones. In addition to that, 25 patients out of the 51 showed school refusal on their course. These symptoms sometimes are accompanied by school refusal. We think that one spectrum is consisted between these symptoms and school refusal. Sleep terror disorder (STD) is rather common in patients with parasomnia, especially between the ages of 3 and 6 years. Main triggering factors at the onset and aggravating factors on course were fear, tension and excitement. Usually patients could not tell any hallucinating contents during the episodes. However, some patients were able to tell the contents to mothers on partial awakening during the episodes and some 'other patients remember a part of the contents after awakening the next morning. We confirmed the contents in 5 patients out of 102 with STD. All the contents of the episodes were accompanied by fear, for example, of ghosts, being killed, monsters and so on. Enuresis is also common in children. A decrease of secretion of antidiuretic hormon during sleep, small contents of bladder and arousal disorders are recognized as main ontogenesis of enuresis. In addition to those, physical and mental stress may play a role in enuresis. In some cases, treatment of enuresis was quite effective by the use of drugs. The enuresis continued to disappear or decrease markedly during and even after the treatment for 2-4 weeks in those cases. This condition may show the role of secondary psychological stress from enuresis itself or some unknown mechanisms of enuresis. Main ontogenesis of tic is thought as diviation of the brain function and abnormality of neurotransmitters. The age of onset was mainly between 3 and 8 years. Main symptoms at the onset were eye blinking, head shaking, twitch of shoulder etc. However, in addition to those symptoms, movement of trunks, arms and legs were seen during the course. The symptoms disappear or decrease in a reverse order in a similar manner when haloperidol or psychological treatment was given. Both treatments were effective for transient tic, but not so effective for Tourette syndrome. We need to clarify those unknown mechanisms.

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At first the importance of differential diagnosis of adolescent psychosomatic diseases from other psychiatric disorders with somatic symptoms was pointed out. Adolescence, like infancy and the terminal stage of life, is the period in which the distance between body and mind is very close, and it is likely that psychosomatic symptoms can develop, even when a certain disorder is not diagnosed as psychosomatic disease (PSD). A correct diagnosis can lead to a correct therapy. If this principle is not applied, there will be a danger of producing iatrogenic diseases. Then, what can the core state of PSD be? For the purpose of clarifying the characteristics of adolescent PSD, the author presented a case of a twelve year old junior high school boy who developed psychogenic fever and consequently was unable to go to school. The conclusions led from this case are as follows : 1. He showed no marked anxieties and conflicts. Neither did he show preoccupation and apprehension with symptoms as in the case of hypochondriasis and obsessional neuroses. Rather, he was overwhelmed by the symptom and maladaptive to the given situations. Thus when free from symptoms, he was never worried about eyes of other friends in going to school. This was quite different from the so-called school refusal in which the patient shows tension and worry. 2. He was very poor at emotional communication to the therapist and showed hardly any deepenig and widening of relationship. He was never hurt by the therapist's words or behaviors in the course of psychotherapy unless some therapeutic change occurred. 3. Clinical history tended to be simple, because he did not oscillate emotionally with the circumstances. In the beginning, he gave an impression that he had a physical disease. 4. However, when his aggression was ventilated, that is, with the breakdown of his defence organization, the world of his fantasy began to appear. This was different from day dream, but it was the world of idol singers and famous baseball players with some colour of reality attached. 5. This was the world which he found it easy to share with his contemporaries. This meant his establishment of the world of contemporary, as well as his independence of the generation of his father, and separation from his parents. This state which the author describes might be quite similar to the so-called alexithymia. But the author wishes to keep the attitude that this state is of different quality from the concept of alexithymia which has the biological basis, because the present patient did not show the concrete thinking and overadaptation. This state characterized by adolescent PSD can be thought to have the genetic factor in the development of pre-adolescence or early adolescence which has the advent of puberty, as well as distortions of parent-child relationship of early childhood. The author thought that the disturbance of delicate and difficult processes of transforming unconscious sensation of body functioning into fantasy in these periods was important. In addition, the author pointed out the importance of taking consideration into the level of personality in the practice of psychosomatic medicine for adolescents.

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[in Japanese]

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As it is not unusual for us to reach age 80 or 90 and older, psychosomatic medicine needs to tackle the problems of this new generation. Medical characteristics of the elderly can be summerized as follows : (1) they are living on the past history of accumulated diseases, (2) symptomatic characteristics are ofen atypical, (3) etiological findings are multifactorial and multidimensional which require dynamic evaluations, (4) physical disorders are apt to cause delirium and psychiatric symptoms. In the elderly, physical symptoms are caused and influenced by psychological problems, particularly by experiences of loss. What have highly developed medical and diagnostic techniques brought about to the elderly? Numerous incurable diseases which had been given up in the past have now become treatable. Also the diagnosis and management of chronic diseases can be made more precisely in general medical facilities. As the result, under these conditions, new problems have occurred in relation to the quality of life in the elderly which lay their lives under strict medical managements ignoring their wills. High-grade technical development naturally has brought about specialization of medicine. Consequently the elderly are more often pronounced to be "abnormal". Their anxiety and distrust in medicine are intensified. We should recognize the importance of each family doctor integrating various kinds of high grade medical information offered by specialists. Finally, the important theme of geriatric medicine today is delirium (acute brain syndrome). Particularly delirium induced by psychological as well as physical and medicational factors must be borne in the minds of all physicians.

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On the clinical aspects of dying patients, we tried to review the history, the present status and the problems, roles and importance of hospices, factors to determine the clinical aspects of death, the relationship with psychosomatic medicine, quality control and assurance, etc. Based on life cycle, the problems of terminal care and medical practice for elderly patients are discussed. (1) In our country, main stream of the terminal medical case is based on the principle to provide the patients with longer life, and the terminal care in hospices is not yet widely developed or propagated .(2) The hospices in Japan, which have been developed under strong influence of hospice movement in Europe and America, are mostly based on palliative care, concentrating on physical care and reflecting cultural and social features of Japan. (3) There are a number of problems in hospice care, including the approach of how to introduce the technical progress in medicine into medical practice. (4) There are many problems related to mental stress. Essentially speaking, the whole person of each patient must be taken into account in the terminal care, and the clinical study of death is closely related to psychosomatic medicine. (5) In the clinical study of death, there are many difficult problems such as the bioethical problem, the problem of informed consent, euthanasia, issues of medical economics, etc. (6) In the clinical study of death, quality control and quality assurance are imporant, and these are the problems to be solved in future. (7) In the problems of life cycle and clinical medicine of death, the death of a patient is involved in the problem specific to his (or her) own generation. For the patient up to middle age, grief care for the bereaved family is more important, while it is more essential for the older patient how to end his (or her) own life.(8) In the clinical care of the older patients, it is essential to maintain the life up to death in comfortable way and to provide assistance to terminate the life in more delicate and dignified manner so that the patient may encounter sound death, the better death, and spiritually elevated death. Musical therapy is useful, and spiritual care is important for this purpose. (9) A patient cannot die in a manner different from the way, in which he (or she) has been living. A patient can be cared only in the same manner as he (or she) has been living. A patient can be cared only in a manner suitable for his (or her) own personaiity.

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It is well known that immunological functions are influenced by stressors. Psychological stressors influence also usual behaviors such as eating, exercise and sleep. Therefore, it is important to investigate the effect of these behaviors on the immunological functions. In this paper, we analysed effects of nutrition, starvation, sleep deprivation, restriction or emotional behaviors on immunological functions using animal models. 1) (NZB × NZW) F_1 autoimmune-prone mice which is used for animal models of systemic lupus erythematosus were compared under the influence of different calorie intakes and different calorie sources. When the energy intake was reduced to 60% of the intake of high calorie groups, survival was doubled in high fat diet group and tripled in carbohydrate group compared to that of high calorie groups. Immunological functions were well maintained in low calorie groups. 2) Functions of macrophage or several T cells were enhanced by short-period of starvation in mice . 3) Sleep deprivation for 3 days suppressed several immune functions in rats. 4) Chemotactic activity of macrophages and number of peripheral white blood cells were almost 50% decreased by 24 hr restriction. Chemotactic activity of macrophages was suppressed by injection of ACTH at dose dependent manner in mice. 5) Using unanesthesized mature cats which were implanted electrode in hypothalamus, emotional behaviors such as restlessness, attack, retreat and searching were elicited by stimulation of the hypothalamus. T cell mitogen responses such as PHA were significantly increased with restless. ness and attack, but decreased with retreat and unchanged with searching. B cell mitogen response such as LPS and phagocytosis of neutrophiles were not significantly changed by these behaviors. Therefore, it was suggested that some immunological functions were influenced by emotional behaviors. These results indicate that immunological functions were influenced by various stressors. It depends on the period, degree and method of stressors.

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We have recently reported that interleukin-1 (IL-1), a cytokine produced mainly by activated monocytes and macrophages, protects the gastric mucosa against ulcerogenic stress and that this anti-ulcer action of IL-1 is mediated by the central nervous system. On the basis of these findings, we have proposed the possible existence of an "immune-brain-gut" axis, which may play an important role in the immunoneuroendocrine regulation of gastric mucosal protection. In the present study, we addressed a mechanism whereby IL-1 exhibits its protective action for the gastric mucosa, using male Wistar rats weighing approximately 200 g. Recombinant human ILl β at various doses (1,10 and 100 ng/rat) was i, c, v. administered. Central IL-1 inhibited gastric acid secretion in a dose-related manner in pylorus-ligated rats. This antisecretory action of IL-1 was completely diminished by pretreatment with indomethacin (2 mg/kg, i. p.), a blocker of prostaglandin (PG) biosynthesis. Similarly, the central injection of IL-1 dose-dependently suppressed gastric emptying in conscious rats. Interesting enough, however, the preinjection of indomethacin failed to alter the inhibitory action of IL-1 on gastric emptying, suggesting that the suppressive effects of IL-1 on gastric functions are mediated by different mechanisms, i.e., PG-dependent or PG-independent. Next, we examined the effects of IL-1 in experimental ulcer models : water-immersion restraint stress and intragastric administration of absolute ethanol. Central IL-1 protected the gastric mucosa against both ulcerogenic stimuli. These results suggest that the mucosal protective effects of IL-1 depend largely on its inhibitory actions on gastric secretion and motility, two important aggressive factors in terms of the pathogenesis of ulcer formation, but it is also possible that other mechanisms including the PG system in the stomach may contribute to the anti-ulcer actions of IL-1. All these data imply that gastric ulcer is not simply a local disease in the stomach, but a general disease involving even the immune system, not to mention the brain. We firmly believe that these novel approaches from an immunoneuroendocrine point of view will bring out a breakthrough for a better understanding of the pathogenesis and pathophysiology of stress ulcer, which in turn will lead to the development of new therapeutic strategies.

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From the behavioral point of view, the continuation and aggravation of psychosomatic disorders are thought to be initiated by conditioned responses to aversive or noxious internal and/or external conditioned stimuli (CS). Anxieties and fears that accompany the conditioned response (CR) i. e, conditioned emotional response (CER), intensify the action of CS through a positive feedback loop such that, consequently, the CR is intensified. It is suggested that, after being evoked by the CS which are accompanied by some unconditioned stimuli, the CER can result from any of the following three processes or their interactions. A : Cognitive learning-Wrong cognitive learning or information provokes the patients' anxiety and this results in aggravation and continuation of symptoms. B : Operant learning-Operant behaviors, done by patients to reduce their anxiety or fear, results in aggravation and continuation of symptoms through the operant principle. C : Classical learning-An effect of the incubation phenomenon increases the patients' anxiety and fear and results in aggravation and continuation of symptoms. For the reasons mentiored above, psychosomatic disorders become worse through these three types of learning and become accelerated depending on their interactions. Cases in which the symptoms are continuous and deteriorating because of cognitive and operant learning (types A and B) are best treated by teaching the patient new ways of thinking, while those that are continuous and deteriorating through classical learning (type C) are best treated by teaching the patients how to control their anxiety.

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Based upon the previous findings obtained from the several neurochemical studies wherein the rats were subjected, we have proposed the three main neurochemical mechanisms of onset of psychosomatic disorders. We have employed the in vivo microdialysis method and the simultaneous determination of levels of both noradrenaline (NA) and 3-methoxy-4-hydroxyphenylethyleneglycol sulfate (MHPG-S0_4) , the major metabolite of NA and the indicative of the released NA, in the rat brain regions. When the rats were exposed to the activity-stress paradign wherein they were kept in a runningwheel activity cage consisting of a wire drum activity wheel and adjoining chamber under a foodrestricted feeding schedule for I hour per day, the number of wheel revolutions was markedly and progressively increased and they revealed the severe gastric lesions and finally resulted in death. Under this situation, the very marked increases in NA release exceeding those caused by other chronic stress situations occurred in the extended brain regions. The finding suggests that one of neurochemical mechanisms of onset of psychosomatic disorders might be the excessive increases in the neurotransmitter release caused by stress. We examined whether or not an aggressive biting response could affect the brain NA release during stress exposure. The rats were restrained in the supine position with or without being allowed to bite a wooden stick. The non-biting rats showed the more marked and persistent increases in brain NA release as compared to those in biting rats. It is suggested that the persistent increases in the neurotransmitter release, even if the degree might be within the range caused by the usual stress situation, might be one of the causative mechanisms of the disorders. When young rats (2 months old) and aged rats (18 months old) were exposed to the repeated immobilization stress for 16 hours daily in 6 days, the brain NA release in the aged rats was markedly and persistently increased, however, no such a phenomenon was observed in the young rats. The finding raises a possibility that the excessive and persistent increases in the transmitter release might also be the causative mechanism. These findings suggest that there might be, at least, the three main neurochemical mechanisms related to onset of psychosomatic disorders ; stress-induced increases in the neurotransmitter release might be excessive, persistent, and excessive and persistent.

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