Letters
Blood SIR:
Groups
in Panic Disorder
Substantial
in families,
to the Editor
but
evidence the
One approach
genetic
Ms. A, a 37-year-old
suggests locus,
that
panic
if any,
has
is to study chromosomal
disorder
been
markers
runs
elusive
(1).
such as ABO
blood type or human leukocyte antigen (HLA) in individuals with the illness. In early studies (2-4) investigators found a higher frequency of blood group 0 among patients with manic-depressive illness than among control subjects and a higher frequency of blood group A among unipolar patients. The finding of a relationship of panic disorder with certain blood groups would be a significant step toward understanding the disorder. We incidentally observed that six of eight consecutively admitted patients with panic disorder had type B blood. This finding prompted further inquiry, and data were collected from 45 patients diagnosed as having panic disorder. Of these 45 patients, 14 patients had blood type A, seven had type B, one had type AB, and 23 had type 0. This distribution of blood types was normal compared to that of the general population.
The search
for a genetic
marker
for panic disorder
rological
not
RR,
Noyes
R, Paulus
Arch
Gen
DL, Slymen
Psychiatry
1983;
study
thinking.
lege
Presentation
SIR: Behavioral
functions
changes,
and psychiatric
of Multiple including
abnormalities,
with increasing frequency in patients (1, 2). Except for a single case report
assistance
vocabulary
but
was
She was
or draw a clock. to her condition.
abnormal
of
long
brainstem thyroid sulfatase, ids were
were
was
have been recognized with multiple sclerosis
(3), the literature
mdi-
brought
surprisingly
unable
to Social
She
poor
to copy
cognitive
for
simple
demonstrated
little
functioning
a col-
geometric insight
prompted
with
a full
relaxation
time
in
the
white
matter
of
the
and cerebellum. Results of blood cortisol and tests and levels of vitamin B1, vitamin B12, arylhexosaminidase, and very-long-chain fatty acall normal. HTLV-I, HIV, and VDRL test results
negative.
Ms. A fulfilled Poser’s diagnostic supported definite MS,” having
criteria frontal,
for “laboratory pyramidal, and
posterior column signs, pathological visual evoked potentials, oligoclonal bands in the CSF, and a brain MRI cornpatible with focal demyelination. Her presentation was that of frontal syndrome, with organic personality disorder sup-
ported
by neuropsychological
testing.
The range of cognitive deficits in MS that certain functions, such as conceptual tion, tend to be preferentially impaired in cognitive
her
Neuropsychological testing demonstrated a severe frontal lobe dysfunction, with difficulties in abstraction, concept formation, judgment, and praxis. In addition, there was marked mental slowing and mild attention deficit.
M.D. M.D. M.D. S. C.
cates that multiple sclerosis is usually diagnosed long before the appearance of any cognitive dysfunction (2, 4). We report an unusual case in which a frontal syndrome was the first manifestation of multiple sclerosis.
410
Her
The
of
Sclerosis alterations
She was neglecting
less in activities outside the toward her husband’s cornabout her condition, she had
neurological examination and workup, which disclosed bilateral frontal release signs, mild left-side pyramidal signs, and bilateral vibration loss in her legs. Laboratory studies revealed oligoclonal bands in her CSF. Visual evoked potentials were abnormal. Brain magnetic resonance imaging (MRI) showed generalized atrophy, with
2. Parker JB, Theilie A, Spielberger CD: Frequency of blood types in a homogeneous group of manic-depressive patients. J Ment Sci 1961; 107:936-942 3. Mendlewicz J, Massart-Guiot T, Willmotte J, Fleiss JL: Blood groups in manic-depressive illness and schizophrenia. Dis Nerv Syst 1974; 35:39-41 4. Shapiro RW, Rafaelsen OJ, Ryder LP, Svejgaard A, Sorensen H: ABO blood groups in unipolar and bipolar manic-depressive patients. Am J Psychiatry 1977; 3:197-200
An Unusual
medical
graduate.
forms regard
40:1065-1069
NARESH P. EMMANUEL, R. BRUCE LYDIARD, JAMES C. BALLENGER, Charleston,
disturbance.
remote, and somewhat apathetic, and her thought processes were mildly slowed, with an impaired capacity for abstract
has been
D: A family
or psychiatric
sought
foci
disorder.
to a psychiat-
Services for counseling at her husband’s insistence. The psychiatric liaison to Social Services examined her and found her fully oriented in time and place. Her affect was blunted,
REFERENCES
panic
was referred
household chores, engaging home, and showing indifference plaints. Because of her apathy
disappointing, and our investigation suggests that blood type in panic disorder offers no new leads. However, the discovery of new probes continually raises hopes that a definite genetic marker for panic disorder and other important psychiatric disorders may be found soon.
1. Crow
woman,
nc outpatient clinic by Social Services because of marital difficulties. A college graduate and mother of three young children, she was showing behavioral changes that had started insidiously 6-8 months prior to referral. When questioned, her family reported that she had no history of neu-
case. Organic the diagnosis
personality of multiple
unique,
because
an
peared
to be the
first
are
reporting
careful
workup
overt
young
usually develops years after (2, 4). Our case seems to be
organic
manifestation
this case
neurological
for
disorder sclerosis
in order
personality
disorder
ap-
of multiple
sclerosis.
We
to stress
examination
patients
is broad (5). It appears processes and atten(4), as was true in this
and
presenting
the extensive
with
importance
of
laboratory
behavioral
changes.
Am
J
Psychiatry
149:3,
March
1992
LE1TERS
REFERENCES
Mr.
1 . Rao SM, Leo GJ, Bernardin L, Unverzagt F: Cognitive dysfunction in multiple sclerosis. Neurology 1991; 41:685-691 2. Peterson RC, Kokman E: Cognitive and psychiatric abnormalities in multiple sclerosis. Mayo Clin Proc 1989; 64:657-663 3. Giordano R, Volpe G, Tambato E, Tavolato B: Symptomatic dementia syndrome of multiple sclerosis. Riv Neurol 1982; 52: 24-32 4. Franklin GW, Nelson CM, Filley CM, Heaton RK: Cognitive loss in multiple sclerosis. Arch Neurol 1989; 46:162-1 67 S. Rao SM: Neuropsychology of multiple sclerosis: a critical review. J Clin Exp Neuropsychol 1986; 8:503-542 LEA AVERBUCH-HELLER, ARIEH Y. SHALEV,
M.D. M.D. Z. ABRAMOWITZ, M.D. Jerusalem, Israel
MOSHE
Cyproterone
Acetate
in the Treatment
Medroxyprogesterone
SIR:
duce
aggression
in
acetate patients
and in male schizophrenic to be due to its lowering inhibition
of
with
has
been
temporal
reported lobe
to re-
epilepsy
(1)
action
acetate
brain.
side
insufficiency.
as
here the efficacy of a new competitive inhibitor of anbinding, cyproterone acetate, in three neuroleptic-re-
patients
adrenal
me-
such
report drogen
three
even
However,
effects,
gain,
aggressive to be devoid
and
the
major
male patients. Cyproterone of the side effects we have
consented
We
acetate is conmentioned. All
to the trial.
Mr. A, a 29-year-old man with mild mental retardation and intermittent explosive disorder, had a long history of unpredictable assaults. He was admitted to the hospital because he attempted to set a fire. During this hospitalization aggressive episodes, including verbal and physical assaults
on staff
members,
occurred
almost
every
day
despite
in-
creasing doses of neuroleptic medication. His mean level of aggression was 19 on the Overt Aggression Scale (3). Cyproterone acetate was gradually added to the existing medications (sultopride, 2400 mg/day; levomepromazine,
400 mg/day;
clorazepate,
150 mg/day),
for 13 years.
psychosis,
B, a 30-year-old had shown
Aggression
During
Scale was 23).
The dose of haloperidol
All three acetate
within
patients 3-4
been
tients. Plasma range. Cyproterone
male
testosterone acetate
patients
ventional
Following
droxyprogesterone
acetate
was discontinued
within 2 weeks, tion of cyproterone
Psychiatry
but
for a month,
his condition acetate, 200
I 49:3,
the
March
administration
of
the patient
improved mg/day.
1992
upon
in order
improvement has C did not relapse discontinued 3
remained
Additional studies these preliminary
mod-
in these
have
which
treatment
for some
by con-
an advantage
can induce
of violent results.
patients
pa-
normal
is unmanageable
it would
acetate,
except in the
be a promising
aggressiveness and
effect
side
encountered
over
me-
important are
side
required
to
REFERENCES 1 . Blumer D, Migeon C: Hormone and hormonal agents in the treatment of aggression. J Nerv Ment Dis 1975; 160:127-137 2. O’Connor M, Baker HWG: Depo-medroxy progesterone acetate as an adjunctive treatment in three aggressive schizophrenic patients. Acta Psychiatr Scand I 983; 67:399-403 3. Yudofsky SC, Silver JM, Jackson W, EndicottJ, Williams D: The Overt Aggression Scale for the objective rating of verbal and physical aggression. Am J Psychiatry 1986; 143:35-39 FLORENCE LUCIEN
THIBAUT, COLONNA,
M.D. M.D.
Sotteville-l#{232}s-Rouen, France
Possible
agents
to a dose of 200 mg/day, the within I month. His agThe other medications were was taking only levomepromonths, when cyproterone
on a regimen
to 30 mg/day
major
levels
may
whose
methods,
effects. confirm
No
cases was
loss in two
Interaction
that
Between
an MAO!
may
induce
such
reviewed
a heightened
a state.
I would
the sero-
awareness
of
like to report
a
on a regimen of a monoamine oxidase lithium seemingly developed the seroexposed to 3,4-methylenedioxymeth-
amphetamine (MDMA), a drug stasy.” A review of the literature of a similar
and “Ecstasy”
( 1 ) recently
Sternbach, M.D. and recommended
case
mg/day.
C was placed
was increased
unsuccessful.
weight
azepam,
J
Mr.
responded to treatment with cyproterone weeks, whereas other treatments had pre-
case in which a patient inhibitor (MAOI) plus tonin syndrome when
200
with
on our his ag-
resulting in daily or staff members level on the Overt
to control the psychotic symptoms. The been maintained for 10 months, and Mr. when cyproterone acetate was gradually months ago.
since the age of 10. During the months that he was on our ward, his level of verbal and physical aggression had gradually increased and reached 1 8 on the Overt Aggression Scale in spite of large doses of medications, including levornepromazine, 300 mg/day; carbamazepine, 600 mg/day; and dicyproterone acetate, increased patient showed clear improvement gressive behavior disappeared. gradually reduced until Mr. B mazine, 150 mg/day. After 4
of disorgan-
of psychosis
of cyproterone acetate, increased to a dose of 300 mg/day. His other medications (haloperidol, 20 mg/day; sultopride, 2 g/day; lorazepam, 10 mg/day) were continued. His aggressive behavior was brought completely under control within 8 weeks, but his hallucinations and delusions worsened.
SIR: Harvey tonin syndrome
man with a diagnosis of infantile aggressive and impulsive behavior
a diagnosis history
been hospitalized the previous 3 months,
behavior
Mr.
Am
with
and Mr. A’s aggres-
disappeared within 3-4 weeks. The maintenance dose of cyproterone acetate was 200 mg/day. This improvement has been maintained for 22 months and has permitted the patient to be discharged from the hospital. At this writing, the concurrent neuroleptic medication has been gradually reduced by more than 50% of the initial dose. sive
man
gressive behavior had gradually increased, physical aggression against either himself that led to occasional injuries (his mean
crate
weight
fractory sidered
feminization,
in
has
ward
viously
patients (2). Its efficacy is thought of testosterone levels and competitive
androgen
droxyprogesterone
of Aggression
C, a 40-year-old
ized schizophrenia, had a long unpredictable assaults. He had
EDITOR
TO THE
interaction
of abuse yielded
referred to as “Econe other reported
(2).
Ms. A was an 1 8-year-old woman with bipolar disorder who was treated with lithium carbonate, 1200 mg/day (average serum level=O.7-0.9 meq/liter), and phenelzine, 60 mg/day.
While
at a party,
she consumed
to contain
four doses
relapsed
was purported
resump-
this with three other pected and no untoward
friends, effects.
who Ms.
a glass
of Ecstasy. reported A developed
of juice
that
She shared only the cxmarkedly
411
Blood SIR:
Groups
in Panic Disorder
Substantial
in families,
to the Editor
but
evidence the
One approach
genetic
Ms. A, a 37-year-old
suggests locus,
that
panic
if any,
has
is to study chromosomal
disorder
been
markers
runs
elusive
(1).
such as ABO
blood type or human leukocyte antigen (HLA) in individuals with the illness. In early studies (2-4) investigators found a higher frequency of blood group 0 among patients with manic-depressive illness than among control subjects and a higher frequency of blood group A among unipolar patients. The finding of a relationship of panic disorder with certain blood groups would be a significant step toward understanding the disorder. We incidentally observed that six of eight consecutively admitted patients with panic disorder had type B blood. This finding prompted further inquiry, and data were collected from 45 patients diagnosed as having panic disorder. Of these 45 patients, 14 patients had blood type A, seven had type B, one had type AB, and 23 had type 0. This distribution of blood types was normal compared to that of the general population.
The search
for a genetic
marker
for panic disorder
rological
not
RR,
Noyes
R, Paulus
Arch
Gen
DL, Slymen
Psychiatry
1983;
study
thinking.
lege
Presentation
SIR: Behavioral
functions
changes,
and psychiatric
of Multiple including
abnormalities,
with increasing frequency in patients (1, 2). Except for a single case report
assistance
vocabulary
but
was
She was
or draw a clock. to her condition.
abnormal
of
long
brainstem thyroid sulfatase, ids were
were
was
have been recognized with multiple sclerosis
(3), the literature
mdi-
brought
surprisingly
unable
to Social
She
poor
to copy
cognitive
for
simple
demonstrated
little
functioning
a col-
geometric insight
prompted
with
a full
relaxation
time
in
the
white
matter
of
the
and cerebellum. Results of blood cortisol and tests and levels of vitamin B1, vitamin B12, arylhexosaminidase, and very-long-chain fatty acall normal. HTLV-I, HIV, and VDRL test results
negative.
Ms. A fulfilled Poser’s diagnostic supported definite MS,” having
criteria frontal,
for “laboratory pyramidal, and
posterior column signs, pathological visual evoked potentials, oligoclonal bands in the CSF, and a brain MRI cornpatible with focal demyelination. Her presentation was that of frontal syndrome, with organic personality disorder sup-
ported
by neuropsychological
testing.
The range of cognitive deficits in MS that certain functions, such as conceptual tion, tend to be preferentially impaired in cognitive
her
Neuropsychological testing demonstrated a severe frontal lobe dysfunction, with difficulties in abstraction, concept formation, judgment, and praxis. In addition, there was marked mental slowing and mild attention deficit.
M.D. M.D. M.D. S. C.
cates that multiple sclerosis is usually diagnosed long before the appearance of any cognitive dysfunction (2, 4). We report an unusual case in which a frontal syndrome was the first manifestation of multiple sclerosis.
410
Her
The
of
Sclerosis alterations
She was neglecting
less in activities outside the toward her husband’s cornabout her condition, she had
neurological examination and workup, which disclosed bilateral frontal release signs, mild left-side pyramidal signs, and bilateral vibration loss in her legs. Laboratory studies revealed oligoclonal bands in her CSF. Visual evoked potentials were abnormal. Brain magnetic resonance imaging (MRI) showed generalized atrophy, with
2. Parker JB, Theilie A, Spielberger CD: Frequency of blood types in a homogeneous group of manic-depressive patients. J Ment Sci 1961; 107:936-942 3. Mendlewicz J, Massart-Guiot T, Willmotte J, Fleiss JL: Blood groups in manic-depressive illness and schizophrenia. Dis Nerv Syst 1974; 35:39-41 4. Shapiro RW, Rafaelsen OJ, Ryder LP, Svejgaard A, Sorensen H: ABO blood groups in unipolar and bipolar manic-depressive patients. Am J Psychiatry 1977; 3:197-200
An Unusual
medical
graduate.
forms regard
40:1065-1069
NARESH P. EMMANUEL, R. BRUCE LYDIARD, JAMES C. BALLENGER, Charleston,
disturbance.
remote, and somewhat apathetic, and her thought processes were mildly slowed, with an impaired capacity for abstract
has been
D: A family
or psychiatric
sought
foci
disorder.
to a psychiat-
Services for counseling at her husband’s insistence. The psychiatric liaison to Social Services examined her and found her fully oriented in time and place. Her affect was blunted,
REFERENCES
panic
was referred
household chores, engaging home, and showing indifference plaints. Because of her apathy
disappointing, and our investigation suggests that blood type in panic disorder offers no new leads. However, the discovery of new probes continually raises hopes that a definite genetic marker for panic disorder and other important psychiatric disorders may be found soon.
1. Crow
woman,
nc outpatient clinic by Social Services because of marital difficulties. A college graduate and mother of three young children, she was showing behavioral changes that had started insidiously 6-8 months prior to referral. When questioned, her family reported that she had no history of neu-
case. Organic the diagnosis
personality of multiple
unique,
because
an
peared
to be the
first
are
reporting
careful
workup
overt
young
usually develops years after (2, 4). Our case seems to be
organic
manifestation
this case
neurological
for
disorder sclerosis
in order
personality
disorder
ap-
of multiple
sclerosis.
We
to stress
examination
patients
is broad (5). It appears processes and atten(4), as was true in this
and
presenting
the extensive
with
importance
of
laboratory
behavioral
changes.
Am
J
Psychiatry
149:3,
March
1992
LE1TERS
REFERENCES
Mr.
1 . Rao SM, Leo GJ, Bernardin L, Unverzagt F: Cognitive dysfunction in multiple sclerosis. Neurology 1991; 41:685-691 2. Peterson RC, Kokman E: Cognitive and psychiatric abnormalities in multiple sclerosis. Mayo Clin Proc 1989; 64:657-663 3. Giordano R, Volpe G, Tambato E, Tavolato B: Symptomatic dementia syndrome of multiple sclerosis. Riv Neurol 1982; 52: 24-32 4. Franklin GW, Nelson CM, Filley CM, Heaton RK: Cognitive loss in multiple sclerosis. Arch Neurol 1989; 46:162-1 67 S. Rao SM: Neuropsychology of multiple sclerosis: a critical review. J Clin Exp Neuropsychol 1986; 8:503-542 LEA AVERBUCH-HELLER, ARIEH Y. SHALEV,
M.D. M.D. Z. ABRAMOWITZ, M.D. Jerusalem, Israel
MOSHE
Cyproterone
Acetate
in the Treatment
Medroxyprogesterone
SIR:
duce
aggression
in
acetate patients
and in male schizophrenic to be due to its lowering inhibition
of
with
has
been
temporal
reported lobe
to re-
epilepsy
(1)
action
acetate
brain.
side
insufficiency.
as
here the efficacy of a new competitive inhibitor of anbinding, cyproterone acetate, in three neuroleptic-re-
patients
adrenal
me-
such
report drogen
three
even
However,
effects,
gain,
aggressive to be devoid
and
the
major
male patients. Cyproterone of the side effects we have
consented
We
acetate is conmentioned. All
to the trial.
Mr. A, a 29-year-old man with mild mental retardation and intermittent explosive disorder, had a long history of unpredictable assaults. He was admitted to the hospital because he attempted to set a fire. During this hospitalization aggressive episodes, including verbal and physical assaults
on staff
members,
occurred
almost
every
day
despite
in-
creasing doses of neuroleptic medication. His mean level of aggression was 19 on the Overt Aggression Scale (3). Cyproterone acetate was gradually added to the existing medications (sultopride, 2400 mg/day; levomepromazine,
400 mg/day;
clorazepate,
150 mg/day),
for 13 years.
psychosis,
B, a 30-year-old had shown
Aggression
During
Scale was 23).
The dose of haloperidol
All three acetate
within
patients 3-4
been
tients. Plasma range. Cyproterone
male
testosterone acetate
patients
ventional
Following
droxyprogesterone
acetate
was discontinued
within 2 weeks, tion of cyproterone
Psychiatry
but
for a month,
his condition acetate, 200
I 49:3,
the
March
administration
of
the patient
improved mg/day.
1992
upon
in order
improvement has C did not relapse discontinued 3
remained
Additional studies these preliminary
mod-
in these
have
which
treatment
for some
by con-
an advantage
can induce
of violent results.
patients
pa-
normal
is unmanageable
it would
acetate,
except in the
be a promising
aggressiveness and
effect
side
encountered
over
me-
important are
side
required
to
REFERENCES 1 . Blumer D, Migeon C: Hormone and hormonal agents in the treatment of aggression. J Nerv Ment Dis 1975; 160:127-137 2. O’Connor M, Baker HWG: Depo-medroxy progesterone acetate as an adjunctive treatment in three aggressive schizophrenic patients. Acta Psychiatr Scand I 983; 67:399-403 3. Yudofsky SC, Silver JM, Jackson W, EndicottJ, Williams D: The Overt Aggression Scale for the objective rating of verbal and physical aggression. Am J Psychiatry 1986; 143:35-39 FLORENCE LUCIEN
THIBAUT, COLONNA,
M.D. M.D.
Sotteville-l#{232}s-Rouen, France
Possible
agents
to a dose of 200 mg/day, the within I month. His agThe other medications were was taking only levomepromonths, when cyproterone
on a regimen
to 30 mg/day
major
levels
may
whose
methods,
effects. confirm
No
cases was
loss in two
Interaction
that
Between
an MAO!
may
induce
such
reviewed
a heightened
a state.
I would
the sero-
awareness
of
like to report
a
on a regimen of a monoamine oxidase lithium seemingly developed the seroexposed to 3,4-methylenedioxymeth-
amphetamine (MDMA), a drug stasy.” A review of the literature of a similar
and “Ecstasy”
( 1 ) recently
Sternbach, M.D. and recommended
case
mg/day.
C was placed
was increased
unsuccessful.
weight
azepam,
J
Mr.
responded to treatment with cyproterone weeks, whereas other treatments had pre-
case in which a patient inhibitor (MAOI) plus tonin syndrome when
200
with
on our his ag-
resulting in daily or staff members level on the Overt
to control the psychotic symptoms. The been maintained for 10 months, and Mr. when cyproterone acetate was gradually months ago.
since the age of 10. During the months that he was on our ward, his level of verbal and physical aggression had gradually increased and reached 1 8 on the Overt Aggression Scale in spite of large doses of medications, including levornepromazine, 300 mg/day; carbamazepine, 600 mg/day; and dicyproterone acetate, increased patient showed clear improvement gressive behavior disappeared. gradually reduced until Mr. B mazine, 150 mg/day. After 4
of disorgan-
of psychosis
of cyproterone acetate, increased to a dose of 300 mg/day. His other medications (haloperidol, 20 mg/day; sultopride, 2 g/day; lorazepam, 10 mg/day) were continued. His aggressive behavior was brought completely under control within 8 weeks, but his hallucinations and delusions worsened.
SIR: Harvey tonin syndrome
man with a diagnosis of infantile aggressive and impulsive behavior
a diagnosis history
been hospitalized the previous 3 months,
behavior
Mr.
Am
with
and Mr. A’s aggres-
disappeared within 3-4 weeks. The maintenance dose of cyproterone acetate was 200 mg/day. This improvement has been maintained for 22 months and has permitted the patient to be discharged from the hospital. At this writing, the concurrent neuroleptic medication has been gradually reduced by more than 50% of the initial dose. sive
man
gressive behavior had gradually increased, physical aggression against either himself that led to occasional injuries (his mean
crate
weight
fractory sidered
feminization,
in
has
ward
viously
patients (2). Its efficacy is thought of testosterone levels and competitive
androgen
droxyprogesterone
of Aggression
C, a 40-year-old
ized schizophrenia, had a long unpredictable assaults. He had
EDITOR
TO THE
interaction
of abuse yielded
referred to as “Econe other reported
(2).
Ms. A was an 1 8-year-old woman with bipolar disorder who was treated with lithium carbonate, 1200 mg/day (average serum level=O.7-0.9 meq/liter), and phenelzine, 60 mg/day.
While
at a party,
she consumed
to contain
four doses
relapsed
was purported
resump-
this with three other pected and no untoward
friends, effects.
who Ms.
a glass
of Ecstasy. reported A developed
of juice
that
She shared only the cxmarkedly
411
