AddictionVolume 102, Issue 11 p. 1722-1729 Free Access Conversation with Hiroshi Suwaki First published: 10 October 2007 https://doi.org/10.1111/j.1360-0443.2007.01904.xAboutSectionsPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat In this occasional series we record the views and personal experience of people who have especially contributed to the evolution of ideas in the Journal's field of interest. Hiroshi Suwaki is a Japanese psychiatrist who has made a contribution to alcohol research which has won him international respect. He has done much to build bridges of understanding and friendship between his country and the scientific community of other countries. INTRODUCTION Addiction (A): Hiroshi, you are a distinguished Japanese psychiatrist, but the first thing a westerner will notice on meeting you is that you write and speak extraordinarily good English. How did you attain these skills? Hiroshi Suwaki (HS): Thank you for your compliment. I was born in 1940 in a beautiful town, Kojima, located in the midst of the Seto Inland Sea National Park in the west of Japan. As you know, in August 1945 Japan laid down arms totally from the battle of World War II. A vivid memory around the year of 1945 is that there were many Koreans living together with us along the same street. They were tough people, amid the poverty after World War II, and we Japanese children learned from them how to obtain a little but precious money by rag-collecting or by raising pigs with hogwash. I still remember their names: Chonsu, Mansu and Heigan. In 1946, when I entered primary school, the era was undergoing a drastic transitional period of national ideology throughout Japan, from loyalty for the emperor to democracy. The characteristic portrait of General Douglas MacArthur, the Supreme Commander at that time, with his pipe and sunglasses, is still vividly preserved in my mind. After the War, we often had a chance to meet and talk to westerners, mainly Americans. At the same time, NHK (Japan Broadcasting Corporation) began to send us English conversation programmes on radio. At that stage in Japan, English became a compulsory subject in junior high school (age 12–14, compulsory education). In senior high school (age 15–17, non-compulsory education), English became as important a subject as Japanese and mathematics. In Kojima Senior High School, I joined an English conversation club and sometimes enjoyed talking with overseas American students. Luckily, I won the prize at the English speech contest in Okayama Prefecture at the age of 16. At university school age, I did not particularly practice to improve my English. On the university campus we sometimes saw westerners, but they were relatively few, compared to the present day. A: So you came to the United Kingdom already with a good grounding in the English language. HS: My English at that time was very much limited in its vocabulary and not satisfactory in daily conversation. I think I actually developed my English after the first visit to London in 1978, where Griffith Edwards kindly introduced me to alcoholism treatment units, therapeutic hostels, detoxification centres and so on, in Britain. There, I met Professor Neil Kessel, Dr Brian Hore, Dr W. H. Kenyon and many other prominent people, and I was enlightened from the conversations with them. I think I was also able to develop my English through interviews with these people. A: Do you read poetry or novels in the English language or just stay with the science? HS: Actually I do not read many novels in English, except for some short stories and essays written by Ernest Hemingway, Somerset Maugham, and so on. PERSONAL BACKGROUND AND EARLY TRAINING A: Where in Japan did you grow up? What sort of family background did you have? What was school like in those days? HS: As I have just mentioned, I was born in Kojima (presently, within Kurashiki City). Both my father and mother were primary school teachers, and I had one brother and two sisters. My mother did not have enough time to take care of four children, so we were all brought up by our grandmother. She had a great talent for fashion designing and was a modern lady of progressive character. My grandfather was also a schoolmaster, but died at a relatively young age. My grandmother could reproduce a design from only one glance at a costume, and she was a real pioneer of the sailor-style dress, which became the widespread standard formal dress for schoolboys and girls in Japan. Later, as Kojima developed, this costume was produced there and Kojima is now noted all over Japan as the place for school uniform. She also instructed us grandchildren in the game of ‘Go’ and ‘Shougi’ (Japanese-style chess) and we enjoyed these games. My younger brother graduated from Tokyo University, and later he became professor of American literature at Musashi University, but sadly died at a relatively young age. ‘My grandmother could reproduce a design from only one glance at a costume, and she was a real pioneer of the sailor-style dress, which became the widespread standard formal dress for schoolboys and girls in Japan.’ A: What was school like in those days? HS: In 1946, when I entered primary school, the era was undergoing a drastic transitional period of national ideology. A: What made you choose medicine as a career, and then psychiatry? HS: I think I had already determined to be a clinical physician before high school age. Tekken Ishii, my grandmother's elder brother, was a warm-hearted out-patient clinician in a small town within 1 hour by bus from my house. He graduated from Osaka University Medical School with a top academic record, but he did not choose to continue his career at the Medical School. Rather, he chose to be a practitioner at his native place in Okayama Prefecture. He treated poor people without money or for small gifts, according to their means. In my childhood, grandmother often took me to his house whenever she visited. I think I decided to be a physician at that time. A: What attracted you specifically at that time? HS: Until the internship I had a dream of being a surgeon. At my internship I met Dr Kiyoshi Matsuoka, a multi-talented surgeon, which resulted in the turning-point of my career from dreams of being a surgeon to subsequently becoming a psychiatrist. He had superb surgical skills with a broad range. I worked with him for 1 month and in this short time I was completely overwhelmed by his accurate and dextrous finger movement in his operations on malignant tumours, vascular microsurgery and bone transplantation, from a pelvis to a clavicle. After the operation, it was our common custom to bathe together in a large bathtub in the Japanese style and to enjoy relaxation and conversation. He seemed completely satisfied and happy with his surgical vocation. At that time, I realized I could never be a surgeon with such gifts as Dr Matsuoka had. Actually he was an ideal super-surgeon, but far beyond my ability. A: So how did you get to psychiatry? HS: At the same time in Kochi, I worked once a week in Geshi Hospital and had accommodation and meals there. On that occasion, I met Dr Takamaro Geshi, a unique and prominent psychiatrist interested in alcoholism treatment, and Mr Harushige Matsumura. Mr Matsumura is the first chairman of the All Japan Alcohol Abstinence Society. This fateful encounter with Dr Geshi and Mr Matsumura led me to devote myself thereafter to alcohol-related problems. A year later, I passed the national examination for physicians and visited Professor Nikichi Okumura: he was the director of the Department of Neuropsychiatry, Okayama University Medical School. I then received my standard psychiatric and neurological training there. A: What was the content and orientation of Japanese psychiatry education when you were training? Was your ‘Dr of Medicine’ by thesis, and if so what was the topic? HS: Actually, there are two ways to obtain the qualification of Igaku-Hakase (Doctor of Medicine). One is the 4-year postgraduate course, in which you can choose the theme for a doctoral thesis, either clinical or experimental, consulting a preceptor in the Department of Neuropsychiatry. When the article for a doctoral thesis is acknowledged to be good enough to be presented to the postgraduate educational board, you are entitled to the title of Doctor of Medicine. The other course is to present the paper to the board after 6 years of residency and/or medical staff. During the period, you have to write the paper under the supervision of the instructor. Many physicians who are interested in basic or clinical research per se choose the 4-year postgraduate course. I wanted to be a clinical psychiatrist and my first choice, without hesitation, was the latter course of 6 years pursuing clinical practice. After I had received basic, standard training in the Department of Neuropsychiatry, Okayama University Medical School, I went to Kochi and again worked in Geshi Hospital for 1 year as a psychiatrist. Then I moved back to Okayama, and had a job at Jikei Hospital. Jikei Hospital is a well-known psychiatric teaching hospital in Japan. There, I established a systematic multi-disciplinary treatment approach to Japanese alcoholics including group meetings, Danshukai [a Japanese-style self-help group similar to Alcoholics Anonymous (AA)] and Naikan psychotherapy (introspective psychotherapy derived from the Shinshu Sect of Buddhism). The client reflects upon and examines their past life, picking up one by one their relationships with mother, father, brothers and sisters, friends, teachers, etc. [1]. A: Generally, did psychiatry have high or low prestige when you first entered it, especially in the Japanese medical hierarchy? HS: Fortunately, the era in which I entered psychiatry was a new epoch shifting from an old prestige, such as the first and second departments of internal medicine, or of surgery, into a new field of speciality comparable with plastic surgery, anaesthesiology or neurosurgery. In such a situation, I think psychiatry or neuropsychiatry was newly regenerated as an attractive clinical field, covering a broad range of human life including biological, psychosocial and spiritual areas, for our entire generation. When I entered Okayama University Medical School in 1958 there were 80 classmates in the same grade. Among them, five students, including myself and two students from other medical schools, enrolled as the residents at the Department of Neuro-Psychiatry directed by Professor Nikichi Okumura. EARLY PUBLICATIONS A: So, as early as 1975 you published a sophisticated follow-up study of alcoholic patients[2]. Can you tell us what led you in this particular research direction and what were your main findings? HS: I felt that long-term follow-up documents of alcoholics tell us the real stories of their lives, in which their social life-styles and medical problems coalesce. Besides, when we want to evaluate whether or not our treatment methods are appropriate, conducting adequate and reliable follow-up studies is indispensable. Thus, 105 male alcoholics whom I had treated as physician-in-charge at Jikei Hospital in Okayama Prefecture were followed for an average of 27 months after leaving the hospital. The factors which proved significant to favourable outcomes were: age above 40 years, married state, Naikan therapy and continuation of after-care by group meetings and/or Danshukai (Abstinence Society). Young, single and sociopathic alcoholics were more difficult to treat. They required time and social welfare. This paper inspired similar subsequent follow-up studies by other Japanese psychiatrists. I think this report was a role model to attract them to clinical studies on alcoholism. ‘I felt that long-term follow-up documents of alcoholics tell us the real stories of their lives, in which their social life-styles and medical problems coalesce.’ A: Then in 1979 came a paper on affective disorders in alcoholism[3]. Again, what were your findings? HS: I reported on affective disorders and other related symptoms (atypical, chronic depressive states, suicide and self-destructive behaviours) in 131 Japanese male alcoholics treated by myself at Jikei Hospital. The incidence and clinical characteristics of these results were comparable to those of the United States and Europe. This study was conducted just before 1980, when DSM-III adopted operational diagnostic criteria. We did not use such objective diagnostic criteria in this study. Nowadays I think the scientific validity of this paper was quite low. A: So here you were, as a relatively young man, contributing papers of considerable interest to the research literature. Am I right in thinking that at that time, your work constituted a new direction for Japanese research? Was this work well received? HS: Yes, I think so. Subsequent Japanese follow-up studies from 1975 to 1989 were listed by Dr Imamichi, in a review paper (in the Japanese language) [4]. Many young Japanese psychiatrists became interested in the treatment and rehabilitation of alcoholism thereafter. VISIT TO THE ADDICTION RESEARCH UNIT (ARU) A: In 1978–1979 you were a visiting fellow at the ARU, at the Institute of Psychiatry, London, and I know that you made a very favourable impression on the people who had the privilege of being your academic hosts. What led you to decide, at that time, to come to London? HS: On 21–26 August 1977, the ICAA International Symposium on Alcohol and Drug Dependence was held in Tokyo and Kyoto. There, I noticed Professor Griffith Edwards for the first time; he delivered a very impressive invited lecture: ‘Diagnosis, treatment and rehabilitation of alcoholics’. On this occasion, I myself presented two papers: ‘Naikan therapy to alcoholic patients’ and ‘Danshukai (Abstinence Society) activities in Okayama Prefecture’. In 1978, I could obtain a grant from ‘Nihon Gakujutsu-Shinkoukai’ (the Japanese Society for Research Promotion) to visit overseas institutions, and I wrote a letter immediately to Griffith. A: What was the content for you of the ARU experience personally and professionally? HS: I came to Great Britain in October 1978, and stayed for 6 months. At the ARU, Griffith visited Bethlehem Royal Hospital Alcoholism Treatment Unit every week and talked to the clients on the importance of joining AA. When he visited there, I joined the small meetings to observe how he spoke with the attendants. I also met David Robinson, who was carrying out research on AA, and Ray Hodgson, who I think was interested in the behavioural approach to alcoholics. Margaret Sheehan very kindly arranged my schedules to visit various institutions, clinics and AA groups in Britain. A: What were your leisure experiences during that early visit to London? HS: I enjoyed leisure time in London with my family—my wife, Sachiko and two sons, Mitsuru, aged 7 years and Makoto, aged 5 years. First of all, I bought a used car, as my driver's licence in Japan was applicable in England, and we enjoyed driving tours to the outskirts of London. We rented a flat along the Compton Road in Wimbledon, a safe, quiet and convenient place, close to the station. Our children were graciously accepted into the primary school, even though it was for only a short stay of 6 months. They enjoyed studying and playing with their classmates. A: Could your hosts have been more sensitive to your needs and to any adjustment problems? HS: No problems at all. Actually, I learned a great deal from Britain, not only in the academic field but also in your democratic and accommodating way of daily living. A: Did England seem like a vastly different culture than Japan, or do we exaggerate the differences? HS: As I have said previously, you had a much more mature, accommodating culture, living together in a multi-racial society. I had a strong impression that people in England behave more politely regarding their needs and feelings. KOCHI MEDICAL SCHOOL A: When you returned to Japan, you were appointed Associate Professor at the Kochi Medical School Department of Neuropsychiatry. Can you tell us something about that centre and your work there? What is the role of neuropsychiatry in your country? HS: I understand the word ‘neuropsychiatry’ comes from the abbreviated form of ‘neurology and psychiatry’. In the late 18th century, many of the Japanese pioneers who introduced modern medicine into Japan went to Germany. They brought back to Japan biologically orientated psychiatry influenced by Griesinger, Wernicke, Kraepelin, and so on. Nowadays, however, dynamic psychiatry by Freud, Jung, and so on is also accepted widely in my country. A: You held that position at Kochi from 1979 to 1986, and your published output developed further. You published, for instance, a review in the British Journal of Addiction in which you introduced western readers to Naikan and Danshukai. Please give us some insight into these Japanese treatment approaches. HS: Naikan is translated into ‘self-observation method’, which aims at the spiritual growth of oneself, regardless of any religious sects. Originally, Mishirabe (self-observation) was practised rigorously in a sect of Jhodoshinshuu Buddhism under conditions of fasting and sleep deprivation. Iinobu Yoshimoto modified this method into a practice in which ordinary people are able to take part, including good meals and good sleep. He named this method Naikan. I think this culturally congruent treatment is easily accepted and helpful to indigenous people. Danshukai is translated into ‘Alcohol Abstinence Society (or Group)’. We might be enlightened in a peer group by sharing the common goal of abstinence. A: In 1981 you published a survey of in-patient alcoholics in two prefectures[5]. One of your more striking findings was that nearly half these patients had been in hospital for a year or more. What significance did you attach to these results? HS: This survey was conducted in 1977–1979, when specialized alcoholic treatment units or hospitals still did not prevail across the country, although some pioneering physicians began to implement these units. Most of the alcoholics were admitted into traditional large psychiatric hospitals, and the duration of admission tended to be longer in that period. A: In 1980 you attended an important World Health Organization (WHO) working group in Washington, which attempted to explore the applicability of the dependence syndrome concept to drugs other than alcohol. Was that the first time you had been in the United States? What are your memories of that meeting? HS: Yes, that was my first visit to the United States and I met many other prominent scientists. That was a great experience. Griffith chaired the meeting, and he arranged the report on alcohol- and drug-related problems, which appeared as: ‘Current state of diagnosis and classification in the mental health field’[6]. A: There then followed a paper which saw you working outside the hospital and collaborating with colleagues on a community survey of male drinkers[7]. What fascinated me here was that questionnaires were completed solely by the wives of the subjects. Was there something in the Japanese situation which made that approach appropriate? HS: I think we considered at that time that we could avoid the denial of reality from alcoholics when we asked these questions of their wives. However, wives themselves might possibly deny the realities and I am not sure our procedure was successful, as we do not have any objective measures to support the results. A: In 1982 you were also publishing work on glue-sniffing in Japan[8]. That has been something of a problem in your country for many years? HS: Yes, it has been a quite big problem. Solvents are cheap and easily obtained by juveniles. They could quickly make a dreamy trip towards fantasy by sniffing. A: Then in 1985 came an important paper on alcohol-induced facial flushing in Japanese men[7]. What were your conclusions here? HS: Drinking behaviours and alcohol-induced facial flushing of 1646 Japanese men were analysed from their questionnaires. The results clearly indicated a significant relationship between flushing and various indices of alcohol sensitivity, as well as low rates of alcohol-related problems. Thus, we proposed that alcohol-induced flushing acts as an important inhibitory factor against excessive alcohol use and its consequent alcohol-related problems. ‘The results clearly indicated a significant relationship between flushing and various indices of alcohol sensitivity, as well as low rates of alcohol-related problems.’ A: Were any further international contacts around this time important to you? HS: In October 1985, at Ibaragi in Osaka, Japan, a very interesting international conference was held. Aino Hospital Foundation hosted the International Conference on ‘Recent advances in biomedical aspects of alcohol and alcoholism’. This international meeting really stimulated we Japanese attendees. A: So let us just pause for a moment. These years at Kochi were obviously productive. But how was your research funded? Did you have to conduct your research in your spare time, or were you given good facilities and institutional encouragement? HS: Yes, we have various kinds of grants, not only from the Ministries of Education and Public Welfare. We can also obtain grants from pharmaceutical companies, local institutions and hospitals when we conduct rigorous research. KAGAWA UNIVERSITY MEDICAL SCHOOL A: Then a job move. From 1986 to 1991 you were Professor of Medical Psychology of Kagawa University Medical School. What is the meaning in Japan of the term ‘medical psychology’? HS: Actually, ‘medical psychology’ is a new term, somewhat strange even to us Japanese. My predecessor, Professor Shigeo Takahashi, named his lecture course ‘medical psychology’. I myself also appreciated this term, which could involve a wide range of psychological and social issues freely, separate from biological backgrounds. A: Tell me how much, at that point in your career, you were travelling abroad? Generally, what were your strategies for maintaining international contacts and awareness? HS: After visiting ARU in 1978, I joined the 1979 Rutgers Summer School of Alcohol Studies, recommended by Griffith, which was held in New Brunswick, USA for 3 weeks. I met Dr Maxwell Weisman, a very pleasant, friendly teacher. I do not think I had such a conscious strategy. I just wanted to grasp and understand the overall picture of this gigantic dependence problem, through meeting internationally prominent scientists. A: I note that you have had papers published in several English-language journals. Did you find journals helpful and sympathetic towards a colleague from another country, or do they tend to be obstructive? HS: Until now, I have never experienced unpleasantness from overseas publishers, although it took almost a week for an air-mail letter from Japan to reach European countries in the early 1980s, if my memory is correct. PROFESSOR IN THE DEPARTMENT OF PSYCHIATRY AND NEUROLOGY, KAGAWA A: From 1991 to 2005 you held a chair in the Department of Psychiatry and Neurology. How did your responsibilities change at this juncture? HS: The former professor of this department, Dr Kiyoshi Hosokawa, was promoted to Vice President for Medical Affairs, Kagawa Medical School, and I was appointed to Chief Director of the Department of Psychiatry and Neurology. This department covers a broad range of scientific and educational activities, from basic research and clinical practice to educational activities on local and national levels. In December 1992, 2 years after my appointment, our department had a large full-time personnel of 25 people. A: I am not going to take you through all your continuing publications item by item, or I would be keeping you here all night. But it is evident that at this time, as well as being an active researcher, you were recognized as a reviewer and commentator on an international professional stage. Again, I do not think there was any other Japanese addiction psychiatrist then operating so broadly on this international stage. Did you enjoy those responsibilities? HS: Yes, I did. When we become older, I think our interests tend to shift from making intensive research directly targeting the problem itself to a comprehensive and accurate understanding of an overall problem and its nature and quality. A: I note that at one point you published with Harold Kalant[9]. Who were the people from other countries with whom you most enjoyed professional contact? HS: Besides Griffith and Brian, I remember Nady El-Guabaly (University of Calgary, Canada), Hans Bergman (Karolinska Institute, Sweden) and Nicholas Kozel (National Institute on Drug Abuse, USA). The University of Calgary has been a sister school of the Kagawa Medical School from 1989 to the present. Nady was the director and professor of the department of psychiatry there. Young doctors and researchers of Kagawa Medical School went to Calgary and conducted collaborative research. Of course, I visited Calgary, and Nady came to Kagawa as well. I hear the University of Newcastle upon Tyne in England is also a sister school to Kagawa University Medical School. In 1980 I was sent to the Karolinska Institute in Stockholm for 1 month as an overseas researcher by the Japanese Ministry of Education. There, I met Hans Bergman. Nicholas J. Kozel was the Chief of Epidemiology Studies and Surveillance Branch, Division of Epidemiology and Prevention Research, NIDA, USA. In 1991 he, with Marissa A. Miller, edited a research monograph [10] and again in 1995 he edited a second monograph with Zili Sloboda and Mario De La Rosa [11]. CURRENT RESPONSIBILITIES A: So in 2005 you took up the job of Director of the Addiction Research Unit at the Sankoh Hospital. That sounds like a very appropriate appointment? HS: Yes, I think it is. Dr Masahiro Ichikawa, Director of Sankou Hospital, is a very practical psychiatrist and an excellent general manager of the hospital. Besides, he has treated alcohol-related clients for many years in collaboration with Danshukai. Just before my retirement, I talked with Dr Ichikawa and without hesitation chose to come to Sankoh Hospital and continue my life work on addiction. A: And you continue as a board member of several Japanese learned societies. Can you tell us something about the current role of such societies that deal with drugs and alcohol in your country? HS: I think it would be better to introduce to you here to the contents of my invited lecture: ‘Alcohol education—to whom, on what should we address ourselves?’. The lecture was highly appraised and accepted by the audience at the 24th General Assembly of Japanese Society of Alcohol-related Problems, held in May, 2003, Osaka, Japan. The outline is as follows: 1 In the field of educational and therapeutic activities to alcoholics and their families (including self-help groups)—I believe core concepts in these activities are to facilitate mutually learned relationships and their spiritual growth. 2 As for the education of medical students, physicians and co-medical personnel—learned small-group discussion and joining self-help groups and alcoholism treatment units are important. 3 Of the educational activities at national level, above all I recall the 16th Annual Conference of the Japanese Society of Alcohol-related Problems held in 1994 in Okayama city, over which I presided as the President. There, we had a heated discussion on excluding alcoholic beverages from vending machines in the streets, which provoked public debate regarding a healthy balance between alcohol and society [12]. In 2003, Dr Susumu Higuchi et al. (Kurihama National Hospital, Japan) published an excellent manual for guiding individuals of various professions to handle alcohol-related problems [13]. ‘In the field of educational and therapeutic activities to alcoholics and their families (including self-help groups)—I believe core concepts in these activities are to facilitate mutually learned relationships and their spiritual growth.’ LOOKING BACK, LOOKING FORWARD A: Looking back, how has the place of alcohol changed in Japanese society over your life-time? HS: Memories of my early life are fragmented and episodic, and memories concerning alcohol are very scanty. I was brought up in a family where no one had the custom of regular drinking. Later, my father took a small amount of sake (Japanese rice wine) as an evening drink. My father was a flusher, and my mother a non-flusher. She never drinks except on special occasions. A unique feature is that half the Japanese population exhibit a flushing response to alcohol and cannot tolerate a large amount. Now, I recall a memory that neighbours gathered and enjoyed sake at the Shintou-shrine festival in the rice crop season of autumn. I think there were alcoholics among us even then, but perhaps I overlooked their existence, as I was too young to grasp our exact surroundings. According to nation-wide statistics of alcohol consumption from 1965 to 1995, per capita alcohol consumption in the United States and France had reached a plateau in the early 1980s. In Japan, however, it continued to increase gradually until 1998 and then reached a plateau, spreading among young and female populations.

(1) We prepared a questionnaire modified from that of Edwards, G. et al, to investigate the factors influencing drinking behaviors. Responses of the questionnaire were filled out by the alcoholics, their families, and health care professionals in four psychiatric hospitals having intensive alcoholic rehabilitation programmes. Clinical course of them were traced back for at least two years. (2) We examined the relationship between the course of alcoholism and the differences in perceptions among alcoholics, their families, and health care professionals. (3) We obtained sufficient responses from 76 alcoholics. Those were divided into two groups; one is a group of alcoholics with a history of continuous abstinence of over one year (50 cases), and the other is the group of less than one year of recent abstinence period (26 cases). (4) As the overall results from the participants, items on "self-help group" were favorably responded for the improvement of drinking behavior. Families tend to perceive more sensitively into the internal psychological changes of the alcoholics than the health care professionals, whereas the health care professionals tend to make general and common responses regardless of any alcoholics. We, health care professionals should be aware of such a limit to promote more efficient collaborative works with alcoholics and their families. (5) We compared these two groups ("over one year group" vs. "less than one year group") with regard to their demographic and family backgrounds, clinical features, treatment, self-help group attendance, employment, etc. (6) A significant accordance of responses among three groups (alcoholics, family, health care professionals) was found in the "over one year group" than in the "less than one year group". Such a high level of accordance is considered to reflect a favorable family adaptation along with the recovery from alcoholism, deep understanding on the part of health care professionals, progress in the treatment and in the relationship in a self-help group. (7) As regards the "less than one year" group, it includes more single individuals and less frequent attendances to self-help groups. For this group of alcoholics, group therapy in a smaller group, individualistically oriented approaches for their needs including various supportive resources in the society should be addressed.

The effects of maternal deprivation (MD) during early postnatal life on the brain-derived neurotrophic factor (BDNF) level were investigated in the present study. Wistar rats were assigned to either maternal deprivation or mother-reared control (MRC) groups. MD manipulation was achieved by separating rat pups from their mothers for 3h a day during postnatal days (PND) 10–15. At 16, 20, 30, and 60 days of age, the level of BDNF mRNA in the hippocampal formation of each group was determined using real-time PCR analysis. Early postnatal maternal deprivation of rat pups resulted in a significant increase in body weight at 60 days of age. The expression of BDNF mRNA in the hippocampus was significantly decreased at 16 days of age, and increased at 30 and 60 days of age. These data indicate that even a brief period of maternal deprivation during early postnatal life can affect hippocampal BDNF expression.

There is an increased incidence of schizophrenia-like psychosis in temporal lobe epilepsy (TLE), and several risk factors have been implicated, including the duration of epilepsy and temporal lobe neuropathology. To investigate the biological mechanism of epileptic psychosis, we examined alterations of central dopaminergic systems in the kainate model of TLE. In adult rats, kainate was microinjected into the left amygdala to induce status epilepticus. An indirect dopamine agonist methamphetamine (MAP, 2 mg/kg, i.p.) was administered before and 1 month after the kainate treatment. MAP-induced locomotor activity was significantly enhanced in the kainate group compared with the baseline (pre-kainate) level, which was antagonized by pretreatment with haloperidol. The enhancement of locomotor activity in the kainate group was significantly correlated with the density of hippocampal CA1 neurons. Although the basal extracellular dopamine concentration was significantly lower in the striatum in the kainate group than in the control group (5.5 vs 39.2 fmol/20-min sample), the maximal concentration following MAP administration did not differ between the two groups. These results clearly demonstrate that hypersensitivity of the dopamine systems develops in the chronic phase of the kainate-induced TLE model, which may be responsible for the mechanism of epileptic psychosis.

Background. Sigma, receptors are involved in the pathogenesis of drug abuse. Two polymorphisms (GC-241-240TT and Gln2Pro) in the sigma, receptor gene (SIGMAR1) have been identified. To investigate the role of SIGMAR1 in conveying susceptibility to alcoholism, we performed a functional analysis of polymorphisms in the SIGMAR1 and a case-control study.Methods: We initially screened for polymorphisms in the 5'-upstream region. The effects of the polymorphisms on transcriptional activity were determined using a gene reporter assay. The distribution of SIGMAR1 polymorphisms was analyzed in 307 alcoholic and 302 control subjects.Results: A novel T-485A polymorphism was identified. The transcriptional activity of the A-485 allele and the TT-241-240 allele was significantly reduced compared with that of the T-485 allele and the GC-241-240 allele. The frequencies of the A-485 allele (chi(2) = 5.575, df = 1, p = .0205) and the TT-241-240/Pro2 haplotype (chi(2) = 21.464, df = 1, p < .0001) were significantly higher in control subjects compared with alcoholic subjects.Conclusions: The T-485A and the GC-241-240TT may be functional polymorphisms, and the A-485 allele and TT-241-240/Pro2 haplotype are possible protective factors for the development of alcoholism. (C) 2004 Society of Biological Psychiatry.

Several pharmacological studies suggest the possible involvement of sigma(1) receptors in the pathogenesis of schizophrenia. An association has been reported between schizophrenia and two variants (GC-241-240TT and Gln2Pro) in the sigma(1) receptor gene (SIGMAR1). We also previously reported that, along with T-485 A, these two variants alter SIGMAR1 function. To investigate the role of SIGMAR1 in conveying susceptibility to schizophrenia, we performed a case-control study. We initially screened for polymorphisms in the SIGMAR1 coding region using PCR-single strand conformation polymorphism analysis. The distribution of SIGMAR1 polymorphisms was analyzed in 100 schizophrenic and 104 control subjects. A novel G620A variant was detected in exon4. G620A was predicted to alter the amino acid represented by codon 211 from arginine to glutamine. Our case-control study showed no significant association between the T-485 A, GC-241-240TT, Gln2Pro, and G620A (Arg211Gln) variants and schizophrenia and clinical characteristics. These findings suggest that these SIGMAR1 variants may not affect susceptibility to schizophrenia.

Kindling of the ventral tegmental area (VTA), a major source of the mesolimbic dopamine pathway, was examined in rats. We applied two quantitative measurements of dopamine sensitivity before and 2 weeks after VTA kindling (20 times electrical stimulations (100 microA at 1 min intervals) delivered once per day for 14 consecutive days): behavioral responses induced by test VTA stimulation and methamphetamine (MAP)-induced locomotor activity. The total amount of MAP-induced locomotor activity was significantly increased after VTA kindling, while the responses to electrical stimulation were unchanged. These results indicate that repeated activation of the mesolimbic dopamine system can produce a neuroplastic change, which results in dopamine supersensitivity.

側頭葉てんかんにおける海馬歯状回顆粒細胞新生の病理学的意義に関して、ラットのカイニン酸扁桃核局所注入モデルを用いて研究した。海馬歯状回顆粒細胞層におけるbromodeoxyuridine陽性細胞数を免疫組織化学法で検出し、CA1、CA3領域における細胞脱落も評価した。カイニン酸投与による辺縁系発作重積の5日後には両側海馬における歯状回前駆細胞の分裂が著明に増加し、その後のシナプス再構成などてんかん原性変化の成因となる可能性が示唆された。NMDA受容体拮抗薬であるMK-801（1mg/kg, i. p.）の単回前処置では、カイニン酸投与後のneurogenesis現象に影響が見られなかった。しかし、MK-801を3回投与した場合には軽度の抑制効果がみられた。一方、MK-801投与がCA1錐体細胞脱落に対して選択的な細胞保護効果を示すことが確認された。以上より、神経細胞脱落は顆粒細胞のneurogenesis促進に必須ではなく、NMDA受容体の活性化が部分的に関与するものと結論された。

N -methyl-D-aspartate (NMDA) receptor dysfunction is involved in the pathogenesis of schizophrenia. We determined the nucleotide sequence of the 5′-upstream region of the human NMDA receptor 2B (NR2B) subunit gene and identified a novel T-200G variant located in one of the Sp1 binding sites. To investigate the effect of this variant on the transcriptional activity of the hNR2B gene, we performed gene reporter assays using PC12 pheochromocytoma cells transiently transfected with luciferase reporter plasmids. In the absence of nerve growth factor (NGF), luciferase activities did not significantly differ between the two alleles and the control plasmid. However, luciferase reporter activity of the T allele was significantly up-regulated compared to that of the G allele in the presence of NGF ( P = 0.0013), indicating that this polymorphic site is a critical region for NR2B gene regulation through NGF-induced Sp1-binding. A case control study showed that the frequency of the G allele ( P = 0.0164) was significantly higher in 100 schizophrenics than in 100 controls. These findings suggest that the T-200G variant causes dysfunction of NMDA receptors consisting of the NR2B subunit and may be involved in the development of schizophrenia. Replication studies of independent samples and family-based association studies are necessary to further evaluate the significance of our findings.

To characterize the biochemical mechanism of cell death induced by ethanol intoxication, we examined expression of mRNAs of bcl-2 and bax genes in the brain, which are related to apoptosis, by using the reverse transcription-polymerase chain reaction method (RT-PCR). According to ethanol administrations, the expression of bcl-2 mRNA in the cerebral cortex decreased after 1 day and be recovered after 3 days. The expression of bcl-2 mRNA in the cerebellum was not changed soon after 1 day and increased after 3 days. The expression of bax mRNA in the cerebral cortex decreased after 1 day and be recovered after 3 days. The expression of bax mRNA in the cerebellum increased after 1 day and after 3 days. We found that bcl-2 or bax mRNA expressions in the brain were changed after short-term ethanol exposure. These results suggest that bcl-2 or bax may have functional significance about ethanol intoxication.

In 1980s, abuse and dependence of BRON-W syrup (cough suppressant), which contains methylephedrine, dihydrocodeine, chlorpheniramine and caffeine, were prevalent in Japan. Pharmacological and clinical studies suggest that methylephedrine and dihydrocodeine cause dependence. Although BRON-L syrup, newly modified cough suppressant contains only chlorpheniramine and caffeine, there still are abuse and dependence of this drug. In this report, three cases of BRON-L syrup abuse are demonstrated. All cases started using BRON-L syrup in the late teens in their peer groups, and dropped out from school. Case 1 misused only BRON-L syrup, but case 2 and 3 were multi-drug abusers (case 2: amphetamine, cocaine, and marijuana, case 3: solvent, alcohol, bromovalerylurea), and had kept in tough with the peer groups. Case 2 and 3 hospitalized more than 2 times. Withdrawal symptoms, such as headache, insomnia, and irritability were mild and improved in a few weeks after drug use was stopped. These findings suggest that 1) psychosocial backgrounds of these cases are in common with those of BRON-W syrup abusers, but 2) the clinical course and prognosis of multi-drug abusers are different from the BRON single abuser, 3) chlorpheniramine and caffeine possibly cause dependence, 4) abusers are likely to choose BRON brand although two main dependence-producing constituents are removed from it now. Therefore, prevention and care of BRON-L abusers requires both psychosocial and pharmacological aspects.

Since delusional disorder is characterized by mono-symptomatic paranoid symptoms, it can be a good clinical model for investigating the dopaminergic mechanism responsible for paranoid symptoms. We examined neuroleptic responses, plasma homovanillic acid (pHVA) and genes of the dopamine receptor (DR) and its synthesizing enzyme (tyrosine hydroxylase: TH) in patients with delusional disorder and compared them with those of schizophrenic patients and healthy controls. Results: (1) A relatively small dose of haloperidol was more effective for delusional disorder than for schizophrenia. (2) The pretreatment level of pHVA was higher in patients with persecution-type, but not in those with jealousy-type delusional disorder, compared with age- and sex-matched controls. This increased pHVA level was decreased eight weeks after successful haloperidol treatment. (3) The genotype frequency of the DRD2 gene Ser311Cys was significantly higher in patients with persecution-type delusional disorder (21%), compared with schizophrenic patients (6%) or controls (6%). (4) Patients homozygous for the DRD3 gene Ser9Ser had higher pretreatment levels of pHVA than those heterozygous for Ser9Gly. (v) A significant positive correlation was found between the polymorphic (TCAT) n repeat in the first intron of the TH gene and pretreatment levels of pHVA in delusional disorder. We suggest that delusional disorder, especially the persecution-type, includes a “dopamine psychosis,” and that polymorphism of the DRD2, DRD3 and/or TH gene is part of the genetic basis underlying the hyperdopaminergic state that produces paranoid symptoms. Further studies on a large sample size are required.