LETTERS TO THE EDITOR
Panic Disorder and Anger Attacks some of the angry outbursts. Both symptoms cleared when the dose
To the Editor:
Anxiety disorders of childhood and adolescence are quite common.
A number of researchers have suggested a possible genetic link be-
tween separation anxiety and shyness in childhood and panic disorder-
agoraphobia in adults. However, it is only recently that the possibility
of the existence of panic disorder in prepubertal children has been
raised (Ballenger et aI., 1989; Black and Robbins, 1990). Most of the
cases reported begin in adolescence with occasional retrospective
reports of prepubertal onset. Despite Klein's caution against the use
of retrospective data to diagnose panic attacks in childhood (Klein
and Klein, 1990), several cases of patients diagnosed in childhood
with panic disorder have appeared.
That panic disorder is an important condition to understand for
child psychiatrists can be gleaned from recent reports of comorbidity
with affective disorders in children hospitalized for somatic com-
plaints, confusing the clinical picture in patients with seizure disorders
and neurological conditions, not uncommonly calling forth unneces-
sary neurological work-ups (Hirsch et aI., 1990).
Panic may occur without the subjective feeling of fear and anxiety
(Russell et aI., 1991). And Fava et al. (1990) have reported the possi-
bility of anger attacks as a variant of panic disorder in adults in which
the symptoms of panic appear with angry "outbursts of anger that
[were] perceived to be excessive and grossly out of proportion to
any precipitating psychosocial stressors," but without the subjective
feelings of anxiety. This report is of a child who exhibited spontaneous
panic attacks from age 5, separation anxiety from age 2 1/2, as well as
episodes of severe anger outbursts with symptoms not unlike those
reported by Fava et aI., all of which responded rapidly and dramati-
cally to a low dose of imipramine.
P.G. is a 6-year-old female referred by her psychotherapist after
making little progress in psychotherapy. A dramatic increase in her
symptoms after a March 1990 earthquake was reported. These could
be divided into two types: Clear-cut anxiety reactions, such as being
unable to fall asleep without an adult with her, were the first type.
She would become tense, stiffen, tremble, perspire, and her heart
would pound. These would also occur without a precipitant. The
second was more like a tantrum, involving P.G. running through the
house, slamming doors and being verbally abusive. On occasion, she
would fall to the floor, heart pounding, shaking, moaning, screaming,
and crying, her back arched, her eyes rolled up under her lids, and be
noticeably very angry. After the March 1990 earthquake, she fre-
quently would have attacks of both types, lasting up to 40 minutes,
sometimes more than one per day, and with little or no apparent
provocation. She could offer no explanation for what was happening
and seemed to be "out of it" during most of these episodes.
The family history is positive in that mother had had several panic
attacks followed by the development of a driving phobia several years
previously and a number of such attacks set off by caffeine. The
father's family had a positive history of affective disorders, and his
brother was in jail for killing a policeman.
After a 48-hour ambulatory EEG, during which two to three epi-
sodes occurred, was read as normal, the patient began receiving a
small dose of imipramine, 10 mg at night. When she reached 20 mg,
she became much less negative, less controlling, and even "empathic
to friends." There were no episodes of panic or tantrums over a 10-
month period. During Month 5, her mother reported some increased
tiredness and the dose was lowered to 10 mg. There was a return of
J. Am. Acad. Child Adolesc. Psychiatry, 31:2, March 1992
was increased to 15 mg/day.
We have seen a number of children referred for depression and
oppositional behavior that included angry outbursts, suicidal ideation,
and dysphoric feelings. On closer scrutiny, symptoms of anxiety
emerged that did not dominate the clinical picture. These children
responded fairly rapidly to relatively small doses of imipramine, which
has been shown to be efficacious in treating anxiety disorders in
children.
As with Fava et al.'s patients, these children responded to doses of
tricyclic antidepressants more rapidly than would be expected if they
had major affective disorders and in doses usually thought to be too
low for the treatment of these conditions. In the study by Fava et aI.,
the patients showed a recurrence of their symptoms abruptly after the
discontinuation of the tricyclics, which appeared to be the case with
P.G. when we lowered her dose of imipramine, and the angry outbursts
were not ameliorated by medications usually used to treat these symp-
toms.
This case is reported as a possible example of a prepubertal child
with panic disorder, who may also exhibit the occurrence of angry
outbursts as a panic variant as described by Fava et al. for adults.
Herbert A. Schreier, M.D.
Oakland Children's Hospital
REFERENCES
Ballenger, J. c., Carek, D. J., Steele, J. 1. & Cornish-McTighe, D.
(1989), Three cases of panic disorder with agoraphobia in children.
Am. J. Psychiatry, 146:922-924.
Black, B. & Robbins, D. R. (1990), Panic disorder in children and
adolescents. J. Am. Acad. Child Adolesc. Psychiatry, 29:36-44.
Fava, M., Anderson, K. & Rosenbaum, J. F. (1990), "Anger attacks":
possible variants of panic and major depressive disorders. Am. J.
Psychiatry, 147:867-870
Hirsch, E., Peretti, S., Boulay, C., Sllal, F. & Maton, B. (1990), Poster
session IV: monitoring, surgery, antiepileptic drugs. Epi/epsia,
31:5.
Klein, D. F. & Klein, R. G. (1990), Does panic disorder exist in
childhood? J. Am. Acad. Chi/dAdo/esc. Psychiatry, 29:834 (letter).
Russell, J. L., Kushner, M. G., Beitman, B. D. & Bartles, K. M.
(1991), Nonfearful panic disorder in neurology patients validated
by lactate challenge. Am. J. Psychiatry, 148:361-364.
Suicidality with Clomipramine
To the Editor:
Regarding the continuing discussion of the possible induction of
suicidal ideation or behavior by serotonergic medication, especially
fluoxetine (Fuller and Beasley, 1991; King et aI., 1991a, b), the follow-
ing case describes the appearance of new suicidal ideation in a child
taking another serotonin-uptake-blocking agent, clomipramine.
An 8- year 9-month-old white Roman Catholic male, taking clomip-
ramine for severely distressing obsessive thoughts (primarily blasphe-
mous), experienced partial relief and no side effects at 50 mg/day (1.3
mg/kg/day). After 2 months on this dose, he noted a new symptom,
having to read sentences over and over because of the obsessive
thought that he had not gotten them right. The patient requested an
increase in the dose. Nine days after raising the dose to 75 mg/day
(2.1 mg/kg/day), he noted the abrupt onset of the wish to die. This
occurred after frustrations in sports and with peers that he and his
369
LETTERS TO THE EDITOR
mother agreed he would normally have shaken off without difficulty.
Although he had some history of "taking things hard," including
tearfulness, the degree of upset at this time was different. He did not
appear otherwise depressed, nor did he acknowledge depressed or
irritable feelings. He noted that the wish to die persisted: "I couldn't
put it out of my mind." He was distressed at not knowing what to do
about this feeling. In the meantime, he noted a decrease in feeling that
he had to read sentences over and over. Clomipramine was reduced
to 25 mg/day without recurrence of the suicidal ideation during 4
months of follow-up and with complete relief from obsessive and
compulsive symptoms.
The seriousness of the symptom and its relevance to the possible
induction of self-destructive ideation or behavior by fluoxetine make
this report of interest. Although fluoxetine and clomipramine are not
structurally related, they both increase serotonin activity through
blocking reuptake. The possible mechanisms of acute suicidality have
been recently debated by King et al. (l99Ia, b) and by Fuller and
Beasley (1991).
This appears to be the first report of new suicidality in a patient
taking clomipramine.
Gordon Harper, M.D.
The Children's Hospital
Boston, Massachusetts
REFERENCES
Fuller, R. F. & Beasley, C. M., Jr. (1991), Fluoxetine mechanism of
action. J. Am. Acad. Child Adolesc. Psychiatry, 30:849 (letter).
King, R. A., Riddle, M. A., Chappell, P. B., Hardin, M. T., Anderson,
G. M., Lombroso, P. & Scahill, Z. (199Ia), Emergence of self-
destructive phenomena in children and adolescents during fluoxe-
tine treatment. J. Am. Acad. Child Adolesc. Psychiatry, 30: 179-186.
- - Anderson, G. M., Rasmusson, A. & Riddle, M. A. (l99Ib),
Fluoxetine mechanism of action. J. Am. Acad. Child Adolesc. Psy-
chiatry, 30:849-850 (letter).
Autism and Epilepsy: Organic Connections?
To the Editor:
We read with interest the report of Vukicevic and Siegel (1990) on
pervasive developmental disorders in monozygotic twins. We report
a similar case of autism and epilepsy in male monozygotic twins.
Case report: An aunt of the twins' mother suffers from chronic
psychosis and is hospitalized in a psychiatric institution. A brother of
the father has a primary affective disorder. There was probable fetal
damage, as a result of a threatened miscarriage at the 36th week and
complete detachment of the placenta at the 39th week, and definite
neonatal distress. Born by cesarean section, the first twin presented
an Apgar score of 7 at I minute and 9 at 5 minutes; the second
twin had a score of 3 at I minute and 5 at 5 minutes. Psychomotor
development was delayed in both boys, and they did not learn to walk
until 2 years of age. They never learned to speak, and frorv the first
years of life, they displayed the characteristic symptoms of autism:
lack of social interaction and ability to play, stereotyped behaviors,
and so on. The first twin began to have complex partial seizures at
age II, and these recurred monthly. The second twin had a similar
seizure 8 months later, with a single recurrence after 6 months.
Kariotyping with search for fragile X, magnetic resonance imaging,
and tests for abnormalities ofthe sugar, amino acid, and mucopolysac-
charide metabolism revealed nothing abnormal. Only a CT brain scan
revealed signs of atrophy in both twins. EEG showed spike activity
over the temporal and central regions of the left hemisphere, more
evident in the second twin.
Numerous studies have demonstrated a high frequency of epilepsy
370
among autistic subjects (Gillberg and Steffenburg, 1987) and of psy-
chosis among epileptics (McKenna et aI., 1985), but an association of
the two in monozygotic twins is rare. There has been much discussion
of the relations between autism and epilepsy, which seem on the latest
evidence to be the outcome of a common cerebral dysfunction (Olsson
et aI., 1988). Our cases evidence the concordance in the twins of two
pathological conditions (autism and epilepsy), probably of heteroge-
neous genetic origin with different involvement of genetic and nonge-
netic factors in the two patients. In both subjects, there was interaction
between hereditary factors (family history of psychiatric illness) and
homogeneous acquired factors (pre- and perinatal distress). Our report
confirms the data of Vukicevic and Siegel (1990) on the primary
importance of suboptimal factors in the fetal or neonatal periods to
normal neuropsychic development.
Similar remarks apply to the multifactorial pathogenesis of epilepsy,
for it has recently been recognized that genetic factors are involved
even in partial epilepsy (Ottman et aI., 1989). One last point regarding
the EEG abnormalities recorded from the left temporal lobe: a left
temporal EEG focus is considered to be most frequently associated
with psychosis in adults (Perez et aI., 1985).
Prof. Carlo Lenti
Universita Degli Studi Di Milano
Milan, Italy
REFERENCES
Gillberg, C. & Steffenburg, S. (1987), Outcome and prognostic factors
in infantile autism and similar conditions. J. Autism Dev. Disord.,
17:271-275.
McKenna, P. J., Kanej, M. & Parrish, K. (1985), Psychotic syndromes
in epilepsy. Am. J. Psychiatry, 142:895-904.
Olsson, I., Steffenburg, S. & Gillberg, C. (1988), Epilepsy in autism
and autistic-like conditions: a population-based study. Arch. Neu-
ral., 45:666-668.
Ottman, R., Annegers, J. E., Hauser, W. A. & Kurland, L. T. (1989),
Seizure risk in offspring of parents with generalized versus partial
epilepsy. Epilepsia, 30:157-161.
Perez, M. M., Trimble, M. R., Murray, N. M. F. & Reider, I. (1985),
Epileptic psychosis: an evaluation of PSE profiles. Br. J. Psychiatry,
146:155-163.
Vukicevic, J., Siegel, B. (1990), Pervasive developmental disorder
in monozygotic twins. J. Am. Acad. Child Adolesc. Psychiatry,
29:897-900.
Biological Liability in Families with Autism
To the Editor:
Piven et al. (1990, 1991) have provided a well-designed comprehen-
sive study of psychiatric disorders in adult siblings and parents of
autistic probands. Our family history studies support their findings,
extending the findings to second-degree relatives, which strengthens
one hypothesis that some of the psychiatric symptomatology may be
an expression of underlying biological liability in families with autism.
One study was designed using the mother of the autistic probands
as the main informant for autistic probands, siblings, and second-
degree family members, i.e., grandparents, aunts and uncles, nieces
and nephews. Family history was obtained using a family history
questionnaire that included questions pertaining to medical and psy-
chiatric illness, medication usage, and learning disabilities. When a
sibling or other family member was identified, diagnosed, or treated
for psychiatric illness, a first-person structured psychiatric interview,
the Schedule for Affective Disorders and Schizophrenia-Lifetime Ver-
sion (SADS-L) was conducted (Spitzer and Endicott, 1978). Diagno-
ses were made using research diagnostic criteria (Spitzer and Robins,
1978). When family members were deceased or unavailable, a second-
J. Am. Acad. Child Adolesc. Psychiatry, 31:2, March 1992