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JUVENILE MANIC-DEPRESSIVE ILLNESS
JUVENILE MANIC-DEPRESSIVE ILLNESS Clinical and Therapeutic Considerations
Sherman C. Feinstein) M.D. and Edward A. Wolpert) M.D.) Ph.D. Manic-depressive disorder has rarely been considered an illness of the prepubertal child. Although there have been some references to the child in the various textbooks, there has been very little consideration that manic-depressive affective states should appear in childhood with the same concordance that schizophrenia and depression (also considered previously to be adolescent and adult diseases) are now recognized in children. Cohen et al. (1954) studied the adult manic-depressive patient's position in his family, but saw the infancy as normal and the child functioning early in a conforming and repressed fashion, with the breakdown occurring later in life. Arieti (1959) described the childhood of the manic-depressive patient as being traumatized by a drastic sudden change in maternal handling from that of a giving, dutybound mother to one involving considerably less care coupled with great expectations. The child accepts these expectations, but harbors a strong resentment which he learns to repress. This repression, however, interferes with the formation of normal parental introjects and D1'. Feinstein is Directol', Child and Adolescent Psychiatl,)1 Training Pmgram, Institute fOT Psychosomatic and Psychiatric Resem'ch and Training, Michael Reese Hospital and Medical Center, and Clinical Associate P1'Ofessor, Pritzher School of Medicine, University of Chicago. Dr. Wolpert is Director, Clinical Services, Institute for Psychosomatic and Psychiatric Research and Training, Michael Reese Hospital and Medical Center, and Clinical Associate PTOfessol', Pl'itzhel' School of Medicine, Univel'sity of Chicago. Reprints may be l'equested from Dr. Feinstein, Psychosomatic and PsychiatTic Institute, Michael Reese Hospilal and Medical Center, Chicago, Illinois 60616,
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the patient tends to incorporate other objects in the environment (siblings, relatives, friends, etc.) so that peripheral adults become parentlike figures. Anthony and Scott (1960) believe that while the occurrence of manic-depression in early childhood as a clinical phenomenon is yet to be demonstrated, there are good reasons to believe in its existence as a psychodynamic entity. Our speculation is that manic-depressive patients may show specific equivalent behavior in childhood which is the precursor of the thymocYclic personality and the manic and depressive states of the adult, and in some cases manifest a juvenile version of the illness. The classical description of manic-depressive illness is that it is a disease of adulthood with the mean age of the onset of bipolar psychosis at 32 years (Perris, 1969) . Male patients have an earlier onset (25.5, S.D. = 10.2) compared to females (35.2, g.D. = 11.8), when the first episode is a manic attack. Winokur et al. (1969) state that their data indicate that manic-depressive disease can occur in childhood before the onset of menstruation or pubertal changes, but that whether it occurs in early childhood is still open to question. Redlich and Freedman (1966) define the diagnostic criteria as: (1) there must be a distinct phasic disturbance of affect without intellectual and personality disintegration; (2) the attacks must be well defined; neither very short periods of elation or depression nor lifelong depression or euphoria are characteristic; (3) the presence of other manic-depressive and cyclothymic persons in the family is considered to be of diagnostic value; and (4) precipitating psychogenic factors are not conspicuous. Anthony and Scott (1960) in reviewing the literature on manicdepressive illness in children present the following 10 criteria to be considered in arriving at a diagnosis. Of the 28 cases reviewed, only 3 fulfilled more than 5 criteria, and no case more than 7. The criteria are: 1. Evidence of an abnormal psychiatric state at some time of the illness approximating the classical clinical description; 2. Evidence of a "positive" family history suggesting a manicdepressive diathesis; 3. Evidenc;e of an early tendency to a manic-depressive type of reaction as manifested in: (a) a cyclothymic tendency with gradually increasing amplitude and length of the oscillations; (b) delirious manic or depressive outbursts occurring during pyrexial illness;
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4. Evidence of a recurrent or periodic illness with at least 2 observed episodes; 5. Evidence of a diphasic illness showing swings of pathological dimension; 6. Evidence of an endogenous illness indicating that the phases of the illness show minimal reference to environmental events; 7. Evidence of a severe illness as indicated by the need for inpatient treatment, heavy sedation, electroconvulsive therapy; 8. Evidence of an abnormal underlying personality of an extroverted type; 9. Absence of features of schizophrenia or organic states; 10. The evidence of current, not retrospective assessments. Recent genetic studies seem to indicate that affective disorders are illnesses with a high degree of heritability. Gershon et aI. (1971) believe that genetic factors may express themselves in an inherited vulnerability which increases the likelihood of development of pathological loss reactions in childhood. This would help explain the development of affective disorders when early life experiences seem normal or of minimal stress. Winokur et aI. (1969) also consider manicdepressive states as genetic in origin and suggest that the chromosomal defect may be sex-linked. A major advance in the treatment of the manic-depressive disorders is the present extensive use of lithium carbonate. First described by Cade (1949), who reported that lithium salts seemed efficacious in treating acute affective disorders of the manic-depressive type, lithium now appears equally effective as a prophylactic agent in preventing or minimizing recurrences (Baastrup and Schou, 1967). The drug is considered safe and functions without blunting of perception or intellect (Schou, 1959, 1968; Schlagenhauf et aI., 1966; Kline, 1969) . The common toxic symptoms of fine hand tremor, anorexia, nausea, and diarrhea rapidly disappear if the dosage is reduced (Wolpert and Mueller, 1969). Annell (1969) described the use of lithium in 12 children from the ages of 7 upward. Only 2 adolescent patients (ages 14 and 16) manifested typical signs of a manic state. All others manifested various symptom complexes, but many had histories of manic-depressive illness in their families. The cases selected for that study were characterized by the sudden change between normalcy and depression, or between depression and hyperactivity that has been described as typi-
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cal of the bipolar type of depression found in the manic-depressive psychoses (Perris, 1969) . Annell further reports that most of the children had sleep disorders, night terrors, and frequent vegetative disorders, e.g., stomachaches and headaches. Three patients suffered from encopresis. She concludes that if lithium will help, the results are clearly manifested in 2 weeks; otherwise the medication should be stopped. Whitehead and Clark (1970) gave lithium to hyperactive children and concluded that there was no change in their activity level after 4- to 12-week trials. CASE PRESENTATION The following case history is that of a white girl who was first seen at the age of (December, 1966) by one of the authors and continues under his care at the present time. The history is presented in some detail in an attempt to give a clinical overview of the affective development of the child and her response to the various therapeutic attempts.
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Case History
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Jody was first seen at the age of because of hyperactivity, low frustration tolerance, impulsive and destructive behavior, and an inability to concentrate. She is the second of 3 children of a white, middle-class family. Her mother was a schoolteacher and her father a very successful businessman. Labor was induced after a normal pregnancy and the delivery was uneventful. Jody was described as an extremely active child whose care was considered difficult. She slept in short spurts and ate poorly. She was well coordinated, crawled early and efficiently, and was difficult to contain in playpens and behind portable gates. She walked at 14 months and was described as hyperactive, impulsive, and uncontrollable. From the age of 6 months, Jody was frequently ill with upper respiratory infections and secondary involvement of the chest, eyes, throat, and ears. There was some suspicion that she might have cystic fibrosis, but after much medical consultation and testing, to which she reacted poorly, this possibility was ruled out. However, because of
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impaired resistance to infection, the patient was kept on antibiotics for a year. Because of her recognizable emotional difficulties, Jody was evaluated psychiatrically at the age of 2. The psychiatrist wrote: A hyperactive, distractible, nonmolding child who stiffened and leaned away from holding and cuddling. Mother, however, was in close contact and concerned. Jody frequently hurts herself and looks "driven." She looks like a waif, is bright and preoccupied with the "good handling" of a doll in play. With mother in the room, Jody became frozen, discouraged, and lost interest in play. The mother noticed that Jody, at the age of 2, changed moods very rapidly. Suddenly, while playing and without apparent reason, she would hit, bite, scratch, and become very destructive. On one occasion, mother was reading J ody a story and J ody suddenly turned and bit her. During these occasional periods of irrational behavior she responded to no one and was very destructive, tearing up bedspreads and writing on walls. Some years later, when a friend bought a coat exactly like hers, she removed it from the coat room at school and cut it up. At other times Jody was likable, warm, friendly and outgoing, and liked to kiss her parents. She had a most difficult time in nursery school and kindergarten in separation and relating to other children, but developed very positive relationships with the teachers, on whom she became very dependent and who saw her as capable and creative. Going to and from school was always difficult, and she insisted on going either with a friend or her sister. If she had to go by herself, she was frequently unable to handle the situation. When frustrated, she would roll around on the floor, flailing her arms and legs, and become extremely difficult to reach verbally. The mother described several incidents in which .Iody started crying, saying that she felt "bad inside" and wished she could die. The mother described a typical behavior episode which occurred on a Thanksgiving Day when J ody was 6 years old: Jody was very excited and wanted to help prepare for the Thanksgiving holiday. She helped set the table, make her bed, and arrange the house. Then she became very creative and made a play Polaroid camera. It was really a sensation, including a 3D-lens, clicker, and flashbulb. Inside the camera she placed many cut-out pictures and drawings. After she took a picture, she would look inside the
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camera for an appropriate picture. She was very stimulated by her activity and went from guest to guest, but as more guests arrived, she became overstimulated and her behavior changed suddenly. She would not "play" with her cousins and became provocative, spoiling the games until she was rejected. She regressed, clung to me, and wanted 100 percent of my attention. She became irritable, wild, and eventually had to be removed from the party.
Family History The parents are young, well-motivated people who have cooperated in the evaluation and treatment. The mother insisted that there was something wrong with Jody, even though she was assured by pediatricians, a child psychiatrist, and a social worker that .I ody was developing normally. It was recommended that mother should get some help because of her unusual expectations and fears during Jody's development. The father is mature, thoughtful, and has a good relationship with his wife and children. He becomes mildly depressed at times, especially during particularly trying family and business demands. The paternal family is described as stable, with no obvious mental disorders. The mother describes herself as a rather thymocyclic individual with her mood swings accentuated when she is fatigued. Her sister manifests wide mood swings and has had some manic psychotic episodes. Both maternal grandparents suffer from severe emotional difficulties. The grandfather is described as a periodic depressive who has been in psychoanalysis for more than 35 years. However, he functions as a creative, very successful individual who has been able to live with his illness. The maternal grandmother is described as a classic manic-depressive with periodic manic and depressive episodes. Currently the grandmother is in a hypomanic state, although in the past year she suffered a severe, incapacitating depression requiring hospitalization. When integrated, she is described as being an energetic, charming, and efficient woman. The mother describes her early life as being rather unstable because of her parents' eccentricities. Her mother was rarely present because of her expansive activities during hypomanic states. In spite of that background, she has a good relationship with her parents, and feels her basic relationship with her husband is solid and mature.
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Psychotherapeutic Course Jody has been seen in weekly psychotherapy since she was 3t years of age. At the time of this presentation (October, 1971) she is l3 years old and continues to be seen regularly. She is a beautiful, delicate, blond child of average size. She relates well, is verbal and expressive, and is very much a participant in the therapeutic process. At the onset of treatment she enjoyed her appointments and played a particular game of her creation with the therapist. She was the princess and the therapist would present various chess pieces at court and ask for forgiveness. She would either grant or reject their wishes. This appeared to be a narcissistic game-an attempt to maintain omnipotence by controlling the therapist. Later she would return to this game when she was upset, and it became a way of communicating her feelings of vulnerability. She was able to describe her depressions and began to understand their relationship to various loss experiences. Concurrent counseling was carried out with both parents, and after several years of ongoing work, there seemed to be some improvement in the overall situation. The original impression was that this hyperactive, immature child had not received adequate mothering, because of the child's enormous needs and the mother's overintellectual approach. A relative anaclitic depressive constellation was thought to have been created against which the child built sadomasochistic defenses. Fixation was at the narcissistic level of ego growth, and the separation-individuation phase of development was not adequately resolved. During one particular appointment, Jody seemed confused and asked why her older sister had come into the waiting room with her. It was explained that her sister was going to start seeing another psychiatrist in the same suite (J ody had previously been told this by her mother) . She seemed very troubled and her mother reported that she was a totally changed child after this appointment. She was agitated, hyperactive, and demanding. Subsequent to this event, she remained in an agitated state for several months, regressing to provocative, destructive behavior. Interpretations of her fears of losing her relationship with her therapist and the resulting depression could not be worked through. Jody appeared to be expansive and hypomanic. She was resistant to free association and regressed in the sessions to the
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princess game. On occasion she drew very elaborate pictures or constructed books of magazine clippings. In school she was destructive, fought, and hurt her peers. She would bite or throw them off their bikes. Previous close friends would be insulted and beaten. After several months of close consultation with the family and the use of tranquilizers, .lody calmed down and resumed her better integrated state, played with her friends, and again related well to her therapist. It was at this point that we began to suspect that we might be dealing with a bipolar, alternating mood state which was rooted in biological vulnerabilities and was triggered by depressive reactions. Several months later after a disappointment, the same process repeated itself and it took several weeks for Jody slowly to reintegrate and to begin functioning again. At this point, when .lody was St, we made a decision to attempt to treat these alternating affective states with lithium carbonate. Federal Drug Administration approval had to be applied for, and a thorough evaluation of her cardiac, renal, and thyroid systems was undertaken. 1 The parents reported that for many years .lody had manifested a periodic "salt hunger" and that she would eat large quantities of table salt. It took almost a year to complete the preparations and in January, 1970 at a point at which Jody cycled into a state of manic behavior, lithium carbonate, 300 mgm. T.LD., was started on an out· patient basis. Within 2 weeks, during which the blood lithium level was monitored every 3 days and the lithium intake adjusted to assure a blood level of 0.6-0.8 Meq/L, a noticeable leveling off of the manic affective state occurred, and the patient was able to resume her usual activities without the destructive, agitated symptoms. In addition, the salt craving seemed to disappear. .lody has remained on lithium 300 mgm. B.LD. for It years and has continued in psychotherapy. There has been no recurrence of the periodic cyclic manic episodes. Instead, we see a child who continues to function well in school and camp. There is a remarkable amount of immaturity still present, but she reacts in a more passive fashion to difficulties and is no longer destructive. She seems to play better in a one-to-one situation than in a group and will occasionally have argu1 Pediatric services were under the direction of Martin J. Kaplan, M.D., Department of Pediatrics, Michael Reese Hospital and Medical Center and Highland Park Hospital, Highland Park, Illinois.
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ments with her girlfriends. There seems to be some affective flattening present, and frequently Jody will not react to situations with her previous spontaneity. However, this situation is gradually improving and her summer camp experience (1971) was a good one, in which she participated actively and with enthusiasm. A recent incident may serve to illustrate her current emotional state, the level of control of affects, and her developing insight. The parents made a decision that the dog which they had been attempting to train unsuccessfully for 9 months should be returned to its previous owners. Jody had disliked this dog and avoided it completely. At the family meeting when the decision was announced, Jody threw herself on the dog, cried, and pleaded that it be spared. She pointed out that she had finally patted him a month previously and would take care of him. The other children, who had a great affection for the dog, and were appropriately unhappy, stared in disbelief. A few hours later, when by prearrangement the owner came to pick up the dog, Jody began to laugh inappropriately and was unable to control her laughter while the others cried and said good-bye. In a subsequent session, she related the incident and explained that losing anything is very difficult for her and that at times she has trouble controlling her feelings when they are very intense. She was beginning to feel comfortable with the dog and wanted only to express the same feelings her siblings had, but they came out in the described fashion. We now believe we are dealing with an example of a juvenile manic-depressive illness. The onset of the illness was recognized before the age of 2 by the mother, but distinct phasic disturbance was not seen until the child was 5t. Prior to this time, distinct, episodic mood shifts with erratic, disintegrative behavior alternated with periods of highly integrated behavior. Intellectual functioning has always remained intact. The affective attacks seem to have been precipitated by loss reactions which overwhelmed the ego and resulted in a shift to affective solutions (Feinstein, 1967) . DISCUSSION This case report was chosen as a preliminary communication from a larger study of affective disorders in children. The diagnosis of manic-
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depressive illness has rarely been considered 2 in very young children, but the specific results from the use of lithium carbonate in the manic-depressive disorders make it necessary to determine the childhood nature of the disease. Early treatment of severe behavioral disorders of childhood may have important implications in the longrange course of the disease in spite of the possible genetic factors. Early manifestations of severe psychic illness interfere with basic child development and result in fixations and deviant characterological structure formation. The criteria usually utilized for the diagnosis of a manic-depressive illness are still deeply influenced by the earlier descriptive studies of Kraeplin and tend to obscure the developmental process which is interfered with by the presence of affective instability. The diagnostic requirement that there should be a distinct and marked phasic disturbance of affect (Redlich and Freedman, 1966) and evidence of a state approximating the classical clinical description (Anthony and Scott, 1960) frequently delays the diagnosis for many years. In the case presented, the concept that we might be dealing with a bipolar
affective disorder did not occur to us until we began to see phasic affective cycling, although the alternating quality of the moods was recognized by the mother very early in the child's life. In another case study of a 14-year-old girl who was seen in an acute psychotic state which responded to psychotherapy, not until 6 years later, when she manifested an acute manic episode which responded dramatically to lithium carbonate, did we make a diagnosis of a manic-depressive illness. This same patient was allowed to discontinue lithium after I year and 3 years later had another manic episode which then forced the authors to insist that she continue taking the drug prophylactically, even when symptom-free. Stone (1971) discusses the difficulties of making a definite diagnosis of a manic-depressive illness and the present tendency to call a patient "schizophrenic till proven otherwise." Winokur et a1. (1969) found many cases of the "schizoaffective" disorders, which are included under the schizophrenias, with a predominance of affective illness among their relatives. Many of these patients later showed clearly recognizable mania. (See also Ziskind et aI., 1971.) Rapidly shifting emotional states in children, which do not seem 2 1'01'
review of reported cases see Anthony and Scott (1960).
Juvenile Manic-Depressive Illness appropriate to the reality stress, should be carefully evaluated as the possible manifestation of a bipolar affective illness, especially if these states tend to remain prolonged and refractive to therapeutic contact. Attacks of manic behavior seem frequently not to obey the criteria of being "well defined" but can begin with a very subtle elevation of affect as a response to a reality situation, are not relieved by the shift in reality, and continue as an endogenously stimulated process. Jody started out Thanksgiving Day (see case history) as enthusiastic and helpful. The way in which she chose to participate stimulated a narcissistic regression, and when overexcited by the multiple demands of her grandiosity, Jody suffered from some inability of the mechanism of repression to control her impulses. A manic state was thus precipitated which lasted several weeks. The presence of affective disorders in close relatives is reported as a very important diagnostic aid by Gershon et al. (1971) and Winokur et al. (1969). Annell (1969) reviewed the literature of manicdepressive illness in children and reports that Kraeplin believed that manic-depressive psychosis might have a genetic component influencing the mentality of the child from earliest infancy. Annell used the history of affective disorders in family members as an indication for lithium therapy in children who presented severe, but undiagnosable clinical pictures. In this case there was no loss or bereavement experience which could explain the anacliticlike affect occasionally manifested by the child. She did have considerable medical treatment from the ages of 6 months to 2 years, but was never hospitalized or separated from her mother. Her mother describes herself as moody and generally hypomanic. Jody has had frequent contact with her maternal grandparents, but never on an extended basis. However, the genetic component in this case must be kept in mind. The mother's insistence that Jody was different and her demand for psychiatric care at the age of 2 seem to indicate a sensitive realization on her part that there was some affective difficulty. The concept that bipolar affective disorders seem to be unrelated to psychogenic factors (Redlich and Freedman, 1966) raises some very important issues. Several of the discrete "manic" episodes in our case study seemed to be precipitated by very specific intrapsychic conflictual situations. The particular episode in which Jody learned that
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her sister was going to receive psychotherapy and mistakenly thought she would lose her therapist led clearly to an acute manic reaction which lasted several months. In her therapy she was able to explain her upset and relate it to feelings of jealousy and competition with her sister. However, being able to understand her error and working through her feelings did not relieve the manic attack. Later, while on lithium, the dog episode which might have triggered an attack did not result in the extended affective reaction of the previous episode. Lidz and Whitehorn (1949) have described the precipitating trauma in thyrotoxicosis as involving' the loss or threat of loss of a cardinal interpersonal relationship. Their description of the early relationships, like those of Cohen et al. (1954) and Arieti (1959), emphasizes the vulnerability of the means for dealing with loss and disappointment. Winnicott (1971) sees manic behavior as denial of a depressive mood. He sees the phasic behavior as being so basic to the character structure that it appears in drawings in the form of two distinct elements in a picture. One can postulate that the affective systems of patients with manicdepressive illness may have a basic vulnerability which, when overstimulated, begins a discharge pattern which does not easily lend itself to autonomous emotional control. The apparent specific effect of lithium carbonate may indicate that some biochemical variation, possibly on a genetic basis, leaves the affective system with a specific vulnerability to affective stress. The occurrence of a depressive reaction to some loss experience may trigger off an affective crisis. The eventual manic crisis may be immediate or delayed by the slow development of first, hypomanic state, leading later to manic attacks. The use of lithium carbonate as an aid in the diagnosis of a manicdepressive illness is circular, but both Annell (1969) and Stone (1971) discuss its use in those diagnostic situations in which a clear set of criteria cannot be developed. The relatively few side effects we have seen in proper lithium utilization make this a feasible procedure. Even though the use of lithium in cases of affective illness frequently leads to a rapid resolution of the manic attack, the importance of concomitant psychotherapy should not be overlooked. If our assumption is correct that the genetic influences leave the mechanisms for dealing with separation and loss in a vulnerable position, the
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value of working psychotherapeutically with the child and the family is inestimable. In the case presented, the affective instability of the child had a deep impact upon the parents' ability to care for her adequately and upon the basic security of her siblings, whom she was capable of hurting severely. An awareness of her vulnerability to loss and separation helped her care somewhat better in these areas, and when cooperation was necessary for the taking of medication and submitting to frequent blood serum tests, the patient was motivated and cooperative.
SUMMARY It is our belief that the example presented of a child with periodic al-
ternating affective disorder is a case of juvenile manic-depressive illness. We postulate that manic-depressive illness appears in early childhood, manifesting itself as erratic, rapidly shifting mood behavior with a basic intactness of intellect. The apparent lack of precipitating trauma may be explained by the enormous sensitivity of these patients to loss or the fear of loss which triggers a distinct, affective episode. The literature describing genetic and biochemical research is discussed. The effectiveness of lithium carbonate makes the early diagnosis of manic-depressive illness necessary. Lithium is a useful drug in the treatment of juvenile manic-depressive illness, and its use is described. Psychotherapy is of great importance in the treatment plan in order to help the child deal with problems of separation-individuation and loss and to help resolve severe fixations which could develop while the child is struggling with the overwhelming psychic trauma of the iJIness and its threat to the ego defenses. The ongoing study will attempt to clarify further the role of loss experiences, the effects of growth and development on the course of the illness, and the longterm results of the psychotherapeutic experience.
REFERENCES [
ANNELL, A. L. (1969), Lithium in the treatment of children and adolescents. Alta Psych. Scand., Supp!., 207:19-30.
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ANTHONY, J. & SCOTT, P. (1960), Manic-depressive psychosis in childhood. ]. Child Psychol. Psychiat., 1:53-72. ARIETI, S. (1959), Manic-depressive psychosis. In: American Handbook of Psychiatry, cd. S. ArietL New York: Basic Books, pp. 419-454. BAASTRUP, P. C. & SCHOU, M. (1967), Lithium as a prophylactic ag'ent: its effect against recurrent depressions and manic-depressive psychosis. Arch. Gen. Psychiat., 16:162-172. CADE, J. 1'. J. (1949), Lithium salts in the treatment of psychotic excitement. Med. ]. Austml., 2:349-352. COHEN, M. B., BAKER, G .. COHEN, R. A., I'ROMM-REICHMANN, F., & WEIGERT, E. V. (1954), An intensive study of twelve ca~es of manic-depressive psychosis. Psychiatry, 17: 103-137. FEINSTEIN, S. C. (1967), Aggression and adolescence. Bull., Chicago Soc. Adotes. Psychiat., I: 1-8. GERSHON, E. S., DUNNER, D. 1... & GOODWIN, F. K. (1971), Toward a biology of affective disorders. Arch. Gen. Psychiat., 25: 1-15. KLINE, N. S. (1969), Lithium: the history of its use in psychiatry. In: Modern Problems in Phannacopsychiatry, 3:75-92. Basel: Karger. LIDZ, T. & WHITEHORN, J. C, (1949), Psychiatric problems in a thyroid clinic. ]. Ame?'. Med. Assn., 139:698-701. PERRIS, C. (1969), The separation of bipolar (manic-depressive) from unipolar recurrent depressive psychoses. Behav. Neuropsychiat., 1(8):17-24. REDLICH, F. C. & FREEDMAN, D. X. (1966), The Theory and Practice of Psychiatry. New York: Basic Books, pp. 533-563. SCHLAGENHAUF, G., TUPIN, J., & WHITE, R. B. (1966), The usc of lithium carbonate in the treatment of manic psychoses. A IIIC>'. }. Psychi,,!., 123:201-206, SCHOU, M. (1959), Lithium in psychiatric therapy: stock-taking after ten years. Psychopharm., 1:65-78. _ (1968), Special review: lithium in psychiatric therapy and prophylaxis. ]. Psychiat. Res., 6:67-95. STONE, M. H. (1971), Mania-a guide for the perplexed. Psychothe?'. Soc. Sci. Rev., 5: 10, 14-18. WHITEHEAD, P. I.. & CLARK, I.. D. (1970), Effect of lithium carbonate, placebo, and thioridazine on hyperactive children. Allie?'. .J. Psychiat., 127:6, 824-825. WINNICOTT, D. W. (1971), TherajJeutic Consultations in Child Psychiatry. London: Hogarth Press. WINOKUR, G., CLAYTON, P . .l" & REICH, T. (1969), Manic DejJressive Illness. St. Louis: Mosby. WOLPERT, E. A. & MUELLER, P. (1969), Lithium carbonate in the treatment of manic-depressive disorders. Arch. Gen. Psychiat., 21: 155-159. ZISKIND, E., SOMERFELD, E., & .lENS, R. (1971) ,Can schizophrenia change to affective psychosis? Amer. ]. Psychiat., 128:331-335.
Sherman C. Feinstein) M.D. and Edward A. Wolpert) M.D.) Ph.D. Manic-depressive disorder has rarely been considered an illness of the prepubertal child. Although there have been some references to the child in the various textbooks, there has been very little consideration that manic-depressive affective states should appear in childhood with the same concordance that schizophrenia and depression (also considered previously to be adolescent and adult diseases) are now recognized in children. Cohen et al. (1954) studied the adult manic-depressive patient's position in his family, but saw the infancy as normal and the child functioning early in a conforming and repressed fashion, with the breakdown occurring later in life. Arieti (1959) described the childhood of the manic-depressive patient as being traumatized by a drastic sudden change in maternal handling from that of a giving, dutybound mother to one involving considerably less care coupled with great expectations. The child accepts these expectations, but harbors a strong resentment which he learns to repress. This repression, however, interferes with the formation of normal parental introjects and D1'. Feinstein is Directol', Child and Adolescent Psychiatl,)1 Training Pmgram, Institute fOT Psychosomatic and Psychiatric Resem'ch and Training, Michael Reese Hospital and Medical Center, and Clinical Associate P1'Ofessor, Pritzher School of Medicine, University of Chicago. Dr. Wolpert is Director, Clinical Services, Institute for Psychosomatic and Psychiatric Research and Training, Michael Reese Hospital and Medical Center, and Clinical Associate PTOfessol', Pl'itzhel' School of Medicine, Univel'sity of Chicago. Reprints may be l'equested from Dr. Feinstein, Psychosomatic and PsychiatTic Institute, Michael Reese Hospilal and Medical Center, Chicago, Illinois 60616,
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the patient tends to incorporate other objects in the environment (siblings, relatives, friends, etc.) so that peripheral adults become parentlike figures. Anthony and Scott (1960) believe that while the occurrence of manic-depression in early childhood as a clinical phenomenon is yet to be demonstrated, there are good reasons to believe in its existence as a psychodynamic entity. Our speculation is that manic-depressive patients may show specific equivalent behavior in childhood which is the precursor of the thymocYclic personality and the manic and depressive states of the adult, and in some cases manifest a juvenile version of the illness. The classical description of manic-depressive illness is that it is a disease of adulthood with the mean age of the onset of bipolar psychosis at 32 years (Perris, 1969) . Male patients have an earlier onset (25.5, S.D. = 10.2) compared to females (35.2, g.D. = 11.8), when the first episode is a manic attack. Winokur et al. (1969) state that their data indicate that manic-depressive disease can occur in childhood before the onset of menstruation or pubertal changes, but that whether it occurs in early childhood is still open to question. Redlich and Freedman (1966) define the diagnostic criteria as: (1) there must be a distinct phasic disturbance of affect without intellectual and personality disintegration; (2) the attacks must be well defined; neither very short periods of elation or depression nor lifelong depression or euphoria are characteristic; (3) the presence of other manic-depressive and cyclothymic persons in the family is considered to be of diagnostic value; and (4) precipitating psychogenic factors are not conspicuous. Anthony and Scott (1960) in reviewing the literature on manicdepressive illness in children present the following 10 criteria to be considered in arriving at a diagnosis. Of the 28 cases reviewed, only 3 fulfilled more than 5 criteria, and no case more than 7. The criteria are: 1. Evidence of an abnormal psychiatric state at some time of the illness approximating the classical clinical description; 2. Evidence of a "positive" family history suggesting a manicdepressive diathesis; 3. Evidenc;e of an early tendency to a manic-depressive type of reaction as manifested in: (a) a cyclothymic tendency with gradually increasing amplitude and length of the oscillations; (b) delirious manic or depressive outbursts occurring during pyrexial illness;
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4. Evidence of a recurrent or periodic illness with at least 2 observed episodes; 5. Evidence of a diphasic illness showing swings of pathological dimension; 6. Evidence of an endogenous illness indicating that the phases of the illness show minimal reference to environmental events; 7. Evidence of a severe illness as indicated by the need for inpatient treatment, heavy sedation, electroconvulsive therapy; 8. Evidence of an abnormal underlying personality of an extroverted type; 9. Absence of features of schizophrenia or organic states; 10. The evidence of current, not retrospective assessments. Recent genetic studies seem to indicate that affective disorders are illnesses with a high degree of heritability. Gershon et aI. (1971) believe that genetic factors may express themselves in an inherited vulnerability which increases the likelihood of development of pathological loss reactions in childhood. This would help explain the development of affective disorders when early life experiences seem normal or of minimal stress. Winokur et aI. (1969) also consider manicdepressive states as genetic in origin and suggest that the chromosomal defect may be sex-linked. A major advance in the treatment of the manic-depressive disorders is the present extensive use of lithium carbonate. First described by Cade (1949), who reported that lithium salts seemed efficacious in treating acute affective disorders of the manic-depressive type, lithium now appears equally effective as a prophylactic agent in preventing or minimizing recurrences (Baastrup and Schou, 1967). The drug is considered safe and functions without blunting of perception or intellect (Schou, 1959, 1968; Schlagenhauf et aI., 1966; Kline, 1969) . The common toxic symptoms of fine hand tremor, anorexia, nausea, and diarrhea rapidly disappear if the dosage is reduced (Wolpert and Mueller, 1969). Annell (1969) described the use of lithium in 12 children from the ages of 7 upward. Only 2 adolescent patients (ages 14 and 16) manifested typical signs of a manic state. All others manifested various symptom complexes, but many had histories of manic-depressive illness in their families. The cases selected for that study were characterized by the sudden change between normalcy and depression, or between depression and hyperactivity that has been described as typi-
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cal of the bipolar type of depression found in the manic-depressive psychoses (Perris, 1969) . Annell further reports that most of the children had sleep disorders, night terrors, and frequent vegetative disorders, e.g., stomachaches and headaches. Three patients suffered from encopresis. She concludes that if lithium will help, the results are clearly manifested in 2 weeks; otherwise the medication should be stopped. Whitehead and Clark (1970) gave lithium to hyperactive children and concluded that there was no change in their activity level after 4- to 12-week trials. CASE PRESENTATION The following case history is that of a white girl who was first seen at the age of (December, 1966) by one of the authors and continues under his care at the present time. The history is presented in some detail in an attempt to give a clinical overview of the affective development of the child and her response to the various therapeutic attempts.
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Jody was first seen at the age of because of hyperactivity, low frustration tolerance, impulsive and destructive behavior, and an inability to concentrate. She is the second of 3 children of a white, middle-class family. Her mother was a schoolteacher and her father a very successful businessman. Labor was induced after a normal pregnancy and the delivery was uneventful. Jody was described as an extremely active child whose care was considered difficult. She slept in short spurts and ate poorly. She was well coordinated, crawled early and efficiently, and was difficult to contain in playpens and behind portable gates. She walked at 14 months and was described as hyperactive, impulsive, and uncontrollable. From the age of 6 months, Jody was frequently ill with upper respiratory infections and secondary involvement of the chest, eyes, throat, and ears. There was some suspicion that she might have cystic fibrosis, but after much medical consultation and testing, to which she reacted poorly, this possibility was ruled out. However, because of
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impaired resistance to infection, the patient was kept on antibiotics for a year. Because of her recognizable emotional difficulties, Jody was evaluated psychiatrically at the age of 2. The psychiatrist wrote: A hyperactive, distractible, nonmolding child who stiffened and leaned away from holding and cuddling. Mother, however, was in close contact and concerned. Jody frequently hurts herself and looks "driven." She looks like a waif, is bright and preoccupied with the "good handling" of a doll in play. With mother in the room, Jody became frozen, discouraged, and lost interest in play. The mother noticed that Jody, at the age of 2, changed moods very rapidly. Suddenly, while playing and without apparent reason, she would hit, bite, scratch, and become very destructive. On one occasion, mother was reading J ody a story and J ody suddenly turned and bit her. During these occasional periods of irrational behavior she responded to no one and was very destructive, tearing up bedspreads and writing on walls. Some years later, when a friend bought a coat exactly like hers, she removed it from the coat room at school and cut it up. At other times Jody was likable, warm, friendly and outgoing, and liked to kiss her parents. She had a most difficult time in nursery school and kindergarten in separation and relating to other children, but developed very positive relationships with the teachers, on whom she became very dependent and who saw her as capable and creative. Going to and from school was always difficult, and she insisted on going either with a friend or her sister. If she had to go by herself, she was frequently unable to handle the situation. When frustrated, she would roll around on the floor, flailing her arms and legs, and become extremely difficult to reach verbally. The mother described several incidents in which .Iody started crying, saying that she felt "bad inside" and wished she could die. The mother described a typical behavior episode which occurred on a Thanksgiving Day when J ody was 6 years old: Jody was very excited and wanted to help prepare for the Thanksgiving holiday. She helped set the table, make her bed, and arrange the house. Then she became very creative and made a play Polaroid camera. It was really a sensation, including a 3D-lens, clicker, and flashbulb. Inside the camera she placed many cut-out pictures and drawings. After she took a picture, she would look inside the
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camera for an appropriate picture. She was very stimulated by her activity and went from guest to guest, but as more guests arrived, she became overstimulated and her behavior changed suddenly. She would not "play" with her cousins and became provocative, spoiling the games until she was rejected. She regressed, clung to me, and wanted 100 percent of my attention. She became irritable, wild, and eventually had to be removed from the party.
Family History The parents are young, well-motivated people who have cooperated in the evaluation and treatment. The mother insisted that there was something wrong with Jody, even though she was assured by pediatricians, a child psychiatrist, and a social worker that .I ody was developing normally. It was recommended that mother should get some help because of her unusual expectations and fears during Jody's development. The father is mature, thoughtful, and has a good relationship with his wife and children. He becomes mildly depressed at times, especially during particularly trying family and business demands. The paternal family is described as stable, with no obvious mental disorders. The mother describes herself as a rather thymocyclic individual with her mood swings accentuated when she is fatigued. Her sister manifests wide mood swings and has had some manic psychotic episodes. Both maternal grandparents suffer from severe emotional difficulties. The grandfather is described as a periodic depressive who has been in psychoanalysis for more than 35 years. However, he functions as a creative, very successful individual who has been able to live with his illness. The maternal grandmother is described as a classic manic-depressive with periodic manic and depressive episodes. Currently the grandmother is in a hypomanic state, although in the past year she suffered a severe, incapacitating depression requiring hospitalization. When integrated, she is described as being an energetic, charming, and efficient woman. The mother describes her early life as being rather unstable because of her parents' eccentricities. Her mother was rarely present because of her expansive activities during hypomanic states. In spite of that background, she has a good relationship with her parents, and feels her basic relationship with her husband is solid and mature.
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Psychotherapeutic Course Jody has been seen in weekly psychotherapy since she was 3t years of age. At the time of this presentation (October, 1971) she is l3 years old and continues to be seen regularly. She is a beautiful, delicate, blond child of average size. She relates well, is verbal and expressive, and is very much a participant in the therapeutic process. At the onset of treatment she enjoyed her appointments and played a particular game of her creation with the therapist. She was the princess and the therapist would present various chess pieces at court and ask for forgiveness. She would either grant or reject their wishes. This appeared to be a narcissistic game-an attempt to maintain omnipotence by controlling the therapist. Later she would return to this game when she was upset, and it became a way of communicating her feelings of vulnerability. She was able to describe her depressions and began to understand their relationship to various loss experiences. Concurrent counseling was carried out with both parents, and after several years of ongoing work, there seemed to be some improvement in the overall situation. The original impression was that this hyperactive, immature child had not received adequate mothering, because of the child's enormous needs and the mother's overintellectual approach. A relative anaclitic depressive constellation was thought to have been created against which the child built sadomasochistic defenses. Fixation was at the narcissistic level of ego growth, and the separation-individuation phase of development was not adequately resolved. During one particular appointment, Jody seemed confused and asked why her older sister had come into the waiting room with her. It was explained that her sister was going to start seeing another psychiatrist in the same suite (J ody had previously been told this by her mother) . She seemed very troubled and her mother reported that she was a totally changed child after this appointment. She was agitated, hyperactive, and demanding. Subsequent to this event, she remained in an agitated state for several months, regressing to provocative, destructive behavior. Interpretations of her fears of losing her relationship with her therapist and the resulting depression could not be worked through. Jody appeared to be expansive and hypomanic. She was resistant to free association and regressed in the sessions to the
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princess game. On occasion she drew very elaborate pictures or constructed books of magazine clippings. In school she was destructive, fought, and hurt her peers. She would bite or throw them off their bikes. Previous close friends would be insulted and beaten. After several months of close consultation with the family and the use of tranquilizers, .lody calmed down and resumed her better integrated state, played with her friends, and again related well to her therapist. It was at this point that we began to suspect that we might be dealing with a bipolar, alternating mood state which was rooted in biological vulnerabilities and was triggered by depressive reactions. Several months later after a disappointment, the same process repeated itself and it took several weeks for Jody slowly to reintegrate and to begin functioning again. At this point, when .lody was St, we made a decision to attempt to treat these alternating affective states with lithium carbonate. Federal Drug Administration approval had to be applied for, and a thorough evaluation of her cardiac, renal, and thyroid systems was undertaken. 1 The parents reported that for many years .lody had manifested a periodic "salt hunger" and that she would eat large quantities of table salt. It took almost a year to complete the preparations and in January, 1970 at a point at which Jody cycled into a state of manic behavior, lithium carbonate, 300 mgm. T.LD., was started on an out· patient basis. Within 2 weeks, during which the blood lithium level was monitored every 3 days and the lithium intake adjusted to assure a blood level of 0.6-0.8 Meq/L, a noticeable leveling off of the manic affective state occurred, and the patient was able to resume her usual activities without the destructive, agitated symptoms. In addition, the salt craving seemed to disappear. .lody has remained on lithium 300 mgm. B.LD. for It years and has continued in psychotherapy. There has been no recurrence of the periodic cyclic manic episodes. Instead, we see a child who continues to function well in school and camp. There is a remarkable amount of immaturity still present, but she reacts in a more passive fashion to difficulties and is no longer destructive. She seems to play better in a one-to-one situation than in a group and will occasionally have argu1 Pediatric services were under the direction of Martin J. Kaplan, M.D., Department of Pediatrics, Michael Reese Hospital and Medical Center and Highland Park Hospital, Highland Park, Illinois.
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ments with her girlfriends. There seems to be some affective flattening present, and frequently Jody will not react to situations with her previous spontaneity. However, this situation is gradually improving and her summer camp experience (1971) was a good one, in which she participated actively and with enthusiasm. A recent incident may serve to illustrate her current emotional state, the level of control of affects, and her developing insight. The parents made a decision that the dog which they had been attempting to train unsuccessfully for 9 months should be returned to its previous owners. Jody had disliked this dog and avoided it completely. At the family meeting when the decision was announced, Jody threw herself on the dog, cried, and pleaded that it be spared. She pointed out that she had finally patted him a month previously and would take care of him. The other children, who had a great affection for the dog, and were appropriately unhappy, stared in disbelief. A few hours later, when by prearrangement the owner came to pick up the dog, Jody began to laugh inappropriately and was unable to control her laughter while the others cried and said good-bye. In a subsequent session, she related the incident and explained that losing anything is very difficult for her and that at times she has trouble controlling her feelings when they are very intense. She was beginning to feel comfortable with the dog and wanted only to express the same feelings her siblings had, but they came out in the described fashion. We now believe we are dealing with an example of a juvenile manic-depressive illness. The onset of the illness was recognized before the age of 2 by the mother, but distinct phasic disturbance was not seen until the child was 5t. Prior to this time, distinct, episodic mood shifts with erratic, disintegrative behavior alternated with periods of highly integrated behavior. Intellectual functioning has always remained intact. The affective attacks seem to have been precipitated by loss reactions which overwhelmed the ego and resulted in a shift to affective solutions (Feinstein, 1967) . DISCUSSION This case report was chosen as a preliminary communication from a larger study of affective disorders in children. The diagnosis of manic-
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depressive illness has rarely been considered 2 in very young children, but the specific results from the use of lithium carbonate in the manic-depressive disorders make it necessary to determine the childhood nature of the disease. Early treatment of severe behavioral disorders of childhood may have important implications in the longrange course of the disease in spite of the possible genetic factors. Early manifestations of severe psychic illness interfere with basic child development and result in fixations and deviant characterological structure formation. The criteria usually utilized for the diagnosis of a manic-depressive illness are still deeply influenced by the earlier descriptive studies of Kraeplin and tend to obscure the developmental process which is interfered with by the presence of affective instability. The diagnostic requirement that there should be a distinct and marked phasic disturbance of affect (Redlich and Freedman, 1966) and evidence of a state approximating the classical clinical description (Anthony and Scott, 1960) frequently delays the diagnosis for many years. In the case presented, the concept that we might be dealing with a bipolar
affective disorder did not occur to us until we began to see phasic affective cycling, although the alternating quality of the moods was recognized by the mother very early in the child's life. In another case study of a 14-year-old girl who was seen in an acute psychotic state which responded to psychotherapy, not until 6 years later, when she manifested an acute manic episode which responded dramatically to lithium carbonate, did we make a diagnosis of a manic-depressive illness. This same patient was allowed to discontinue lithium after I year and 3 years later had another manic episode which then forced the authors to insist that she continue taking the drug prophylactically, even when symptom-free. Stone (1971) discusses the difficulties of making a definite diagnosis of a manic-depressive illness and the present tendency to call a patient "schizophrenic till proven otherwise." Winokur et a1. (1969) found many cases of the "schizoaffective" disorders, which are included under the schizophrenias, with a predominance of affective illness among their relatives. Many of these patients later showed clearly recognizable mania. (See also Ziskind et aI., 1971.) Rapidly shifting emotional states in children, which do not seem 2 1'01'
review of reported cases see Anthony and Scott (1960).
Juvenile Manic-Depressive Illness appropriate to the reality stress, should be carefully evaluated as the possible manifestation of a bipolar affective illness, especially if these states tend to remain prolonged and refractive to therapeutic contact. Attacks of manic behavior seem frequently not to obey the criteria of being "well defined" but can begin with a very subtle elevation of affect as a response to a reality situation, are not relieved by the shift in reality, and continue as an endogenously stimulated process. Jody started out Thanksgiving Day (see case history) as enthusiastic and helpful. The way in which she chose to participate stimulated a narcissistic regression, and when overexcited by the multiple demands of her grandiosity, Jody suffered from some inability of the mechanism of repression to control her impulses. A manic state was thus precipitated which lasted several weeks. The presence of affective disorders in close relatives is reported as a very important diagnostic aid by Gershon et al. (1971) and Winokur et al. (1969). Annell (1969) reviewed the literature of manicdepressive illness in children and reports that Kraeplin believed that manic-depressive psychosis might have a genetic component influencing the mentality of the child from earliest infancy. Annell used the history of affective disorders in family members as an indication for lithium therapy in children who presented severe, but undiagnosable clinical pictures. In this case there was no loss or bereavement experience which could explain the anacliticlike affect occasionally manifested by the child. She did have considerable medical treatment from the ages of 6 months to 2 years, but was never hospitalized or separated from her mother. Her mother describes herself as moody and generally hypomanic. Jody has had frequent contact with her maternal grandparents, but never on an extended basis. However, the genetic component in this case must be kept in mind. The mother's insistence that Jody was different and her demand for psychiatric care at the age of 2 seem to indicate a sensitive realization on her part that there was some affective difficulty. The concept that bipolar affective disorders seem to be unrelated to psychogenic factors (Redlich and Freedman, 1966) raises some very important issues. Several of the discrete "manic" episodes in our case study seemed to be precipitated by very specific intrapsychic conflictual situations. The particular episode in which Jody learned that
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her sister was going to receive psychotherapy and mistakenly thought she would lose her therapist led clearly to an acute manic reaction which lasted several months. In her therapy she was able to explain her upset and relate it to feelings of jealousy and competition with her sister. However, being able to understand her error and working through her feelings did not relieve the manic attack. Later, while on lithium, the dog episode which might have triggered an attack did not result in the extended affective reaction of the previous episode. Lidz and Whitehorn (1949) have described the precipitating trauma in thyrotoxicosis as involving' the loss or threat of loss of a cardinal interpersonal relationship. Their description of the early relationships, like those of Cohen et al. (1954) and Arieti (1959), emphasizes the vulnerability of the means for dealing with loss and disappointment. Winnicott (1971) sees manic behavior as denial of a depressive mood. He sees the phasic behavior as being so basic to the character structure that it appears in drawings in the form of two distinct elements in a picture. One can postulate that the affective systems of patients with manicdepressive illness may have a basic vulnerability which, when overstimulated, begins a discharge pattern which does not easily lend itself to autonomous emotional control. The apparent specific effect of lithium carbonate may indicate that some biochemical variation, possibly on a genetic basis, leaves the affective system with a specific vulnerability to affective stress. The occurrence of a depressive reaction to some loss experience may trigger off an affective crisis. The eventual manic crisis may be immediate or delayed by the slow development of first, hypomanic state, leading later to manic attacks. The use of lithium carbonate as an aid in the diagnosis of a manicdepressive illness is circular, but both Annell (1969) and Stone (1971) discuss its use in those diagnostic situations in which a clear set of criteria cannot be developed. The relatively few side effects we have seen in proper lithium utilization make this a feasible procedure. Even though the use of lithium in cases of affective illness frequently leads to a rapid resolution of the manic attack, the importance of concomitant psychotherapy should not be overlooked. If our assumption is correct that the genetic influences leave the mechanisms for dealing with separation and loss in a vulnerable position, the
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value of working psychotherapeutically with the child and the family is inestimable. In the case presented, the affective instability of the child had a deep impact upon the parents' ability to care for her adequately and upon the basic security of her siblings, whom she was capable of hurting severely. An awareness of her vulnerability to loss and separation helped her care somewhat better in these areas, and when cooperation was necessary for the taking of medication and submitting to frequent blood serum tests, the patient was motivated and cooperative.
SUMMARY It is our belief that the example presented of a child with periodic al-
ternating affective disorder is a case of juvenile manic-depressive illness. We postulate that manic-depressive illness appears in early childhood, manifesting itself as erratic, rapidly shifting mood behavior with a basic intactness of intellect. The apparent lack of precipitating trauma may be explained by the enormous sensitivity of these patients to loss or the fear of loss which triggers a distinct, affective episode. The literature describing genetic and biochemical research is discussed. The effectiveness of lithium carbonate makes the early diagnosis of manic-depressive illness necessary. Lithium is a useful drug in the treatment of juvenile manic-depressive illness, and its use is described. Psychotherapy is of great importance in the treatment plan in order to help the child deal with problems of separation-individuation and loss and to help resolve severe fixations which could develop while the child is struggling with the overwhelming psychic trauma of the iJIness and its threat to the ego defenses. The ongoing study will attempt to clarify further the role of loss experiences, the effects of growth and development on the course of the illness, and the longterm results of the psychotherapeutic experience.
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ANTHONY, J. & SCOTT, P. (1960), Manic-depressive psychosis in childhood. ]. Child Psychol. Psychiat., 1:53-72. ARIETI, S. (1959), Manic-depressive psychosis. In: American Handbook of Psychiatry, cd. S. ArietL New York: Basic Books, pp. 419-454. BAASTRUP, P. C. & SCHOU, M. (1967), Lithium as a prophylactic ag'ent: its effect against recurrent depressions and manic-depressive psychosis. Arch. Gen. Psychiat., 16:162-172. CADE, J. 1'. J. (1949), Lithium salts in the treatment of psychotic excitement. Med. ]. Austml., 2:349-352. COHEN, M. B., BAKER, G .. COHEN, R. A., I'ROMM-REICHMANN, F., & WEIGERT, E. V. (1954), An intensive study of twelve ca~es of manic-depressive psychosis. Psychiatry, 17: 103-137. FEINSTEIN, S. C. (1967), Aggression and adolescence. Bull., Chicago Soc. Adotes. Psychiat., I: 1-8. GERSHON, E. S., DUNNER, D. 1... & GOODWIN, F. K. (1971), Toward a biology of affective disorders. Arch. Gen. Psychiat., 25: 1-15. KLINE, N. S. (1969), Lithium: the history of its use in psychiatry. In: Modern Problems in Phannacopsychiatry, 3:75-92. Basel: Karger. LIDZ, T. & WHITEHORN, J. C, (1949), Psychiatric problems in a thyroid clinic. ]. Ame?'. Med. Assn., 139:698-701. PERRIS, C. (1969), The separation of bipolar (manic-depressive) from unipolar recurrent depressive psychoses. Behav. Neuropsychiat., 1(8):17-24. REDLICH, F. C. & FREEDMAN, D. X. (1966), The Theory and Practice of Psychiatry. New York: Basic Books, pp. 533-563. SCHLAGENHAUF, G., TUPIN, J., & WHITE, R. B. (1966), The usc of lithium carbonate in the treatment of manic psychoses. A IIIC>'. }. Psychi,,!., 123:201-206, SCHOU, M. (1959), Lithium in psychiatric therapy: stock-taking after ten years. Psychopharm., 1:65-78. _ (1968), Special review: lithium in psychiatric therapy and prophylaxis. ]. Psychiat. Res., 6:67-95. STONE, M. H. (1971), Mania-a guide for the perplexed. Psychothe?'. Soc. Sci. Rev., 5: 10, 14-18. WHITEHEAD, P. I.. & CLARK, I.. D. (1970), Effect of lithium carbonate, placebo, and thioridazine on hyperactive children. Allie?'. .J. Psychiat., 127:6, 824-825. WINNICOTT, D. W. (1971), TherajJeutic Consultations in Child Psychiatry. London: Hogarth Press. WINOKUR, G., CLAYTON, P . .l" & REICH, T. (1969), Manic DejJressive Illness. St. Louis: Mosby. WOLPERT, E. A. & MUELLER, P. (1969), Lithium carbonate in the treatment of manic-depressive disorders. Arch. Gen. Psychiat., 21: 155-159. ZISKIND, E., SOMERFELD, E., & .lENS, R. (1971) ,Can schizophrenia change to affective psychosis? Amer. ]. Psychiat., 128:331-335.