Am
J Psychiatry
135:2,
chotic medication family history her movement her prescribed phenidate in symptoms
of
methapyrilene methylphenidate,
She
had
February
1978
CLINICAL
and lithium. There was no personal or of neurologic disease. At least 2 weeks before disorder developed, she had stopped taking medication and had begun to abuse methyldoses of 30-100 mg/day. After developing movement disorder, she had started taking in doses of up to 250 mg/day in addition to the without changes in her symptoms.
marked
choreoathetosis
of all extremities,
responsive to halopenidol, a blocker mine receptors, are consistent with mine hypothesis.
head,
The
have
recurrence
The
pathophysiology and
to involve in the
and
increased
brain
the
(1).
Stimulants
activity, disorders
in hyperkinetic
Clinical
A recent
been
tentiates
such
as
have and
been reported dyskinesias
children
(3). These
of CSF
study
reported
that
mean
are
Nucleotides
BIEDERMAN,
cAMP
values
schizophrenic ues were prognoses
was
significantly
cyclic
greater
in
M.D.,
RANAN
among
sig-
of schizophrenic
ciated
with
poor-prognosis
patients
with
process
high cAMP, schizophrenia.
from
the Scottish
0002-953X/78/0002-0253$0.40
RIMON,
of has
cholinergic
activity.
75:203-212,
1972
M.D.,
The missions rusalem
assoThe
Rite Schizo-
was
period
patient
EBSTEIN,
designed
group
PH.D.,
to systematically
consisted
of drug-free Mental Health
of December
diagnosis trists (1).
evaluate
was No
made patient
of 20 consecutive
ad-
schizophrenic patients Center inpatient unit
to the during
1975
1976.
through
by consensus had received
August oftwo staff neuroleptic
Jethe
The
psychiatreat-
ment for at least 2 weeks prior to admission. Of the 20 patients, 19 had been hospitalized previously and 2 had a 2-year history of illness before his first hospitalization. viously
CSF biochemical data for 10 of the 20 patients
Lumbar CSF was obtained cAMP and cyclic guanosine were measured as described sample
© 1978
RICHARD
Method
the
When this work was done, Drs. Zohar and Biederman were Residents in Psychiatry and Dr. Rimon was Visiting Professor, Jerusa1cm Mental Health Center, Ezrath Nashim, where Dr. Ebstein is Senior Biochemist and Dr. Belmaker is Director of Research. Address reprint requests to Dr. Belmaker at P.O. Box 140, Jerusalem Mental Health Center, Ezrath Nashim, Jerusalem, Israel. This work was supported by a grant phrenia Research Program.
use
Schizophrenia
the
patients, and the two highest cAMP valin schizophrenic patients with notably poor (1). This suggested the existence of a sub-
group
to the influence
HL, Weiner WI: The pharmacology of choreatic disorders. Prog Neurobiol 6:49-80, 1976 0: Psychoses and the punding and choreiform synaddiction to central stimulant drugs. Psychiatr Neurol
present study this hypothesis.
adenosinc
monophosphate (cAMP) levels in the ccrcbnospinal fluid (CSF) of schizophrenic patients do not differ nificantly from those of pneanesthctic psychiatrically normal controls (1). However, the variance of
related
cholinergic
of there
Denckla MB, Bemporad JR. McKay MC: Tics following methylphenidate administration. JAMA 235: 1349-135 1 , 1976 4. Klawans HL, Weiner WJ: The effect of d-amphetamine on choreiform movement disorders. Neurology 24:312-318, 1974 5. Thack IT, Chase TN, Bosma IF: Oral facial dyskinesia associated with prolonged use of antihistaminic decongestants. N EngI J Med 293:486-487, 1975
to (2)
stimulants
antihistaminic/anti-
3.
do-
to lead addicts
dopadopa-
in the development be noted since
of dyskinesias
central
Neurochir
influence
in
Cyclic
ZOHAR, M.D., JOSEPH H. BELMAKER, M.D.
dis-
central
the
Decreased
(5).
1 . Klawans movement 2. Rylander dromes in
methylphenidatc
potentiate
of
of central the above
REFERENCES
hypothesized
neuronal
which
Correlates
BY JOSEPH AND ROBERT
movement
has
dopaminergic
amphetamines,
paminengic chorciform
and
dyskinesias
reports
drugs
of her symptoms.
of chorciform
related
REPORTS
been hypothesized to play a role in choreiform movement disorders (1); however, this patient showed no improvement following physostigmine, a drug that po-
Discussion
orders
role
drug methapyrilene symptoms should
been
these
was then given haloperidol, 4 mg I.M. over 60 minutes. She went to sleep briefly and awoke markedly improved, with only a mild residual movement disorder. She was instructed to take low doses of oral haloperidol for several days. At 1-
she denied
possible
cholinergic this patient’s
She was given physostigmine, 3 mg I.M. over 90 minutes. There was no improvement. and she became nauseated. She
follow-up
RESEARCH
known to exacerbate the symptoms of chorea (4), while dopamine-blocking drugs are known to improve chorciform symptoms (1). The findings in this patient of a choreiform syndrome that was precipitated by methylphenidate, a potentiator of dopamine, and was
and neck, as well as buccal-facial-lingual dyskinesias. The physical exam, which included a neurologic assessment, was otherwise unremarkable except for dry mouth, tachycardia, and sluggish mid-position pupils. She was alert. oriented, and mildly hypomanic. Routine laboratory tests were unremarkable.
month
AND
American
assays Psychiatric
were
done Association
had been (1).
and cyclic monophosphate previously
in a single
batch
reported
pre-
nucleotides, (cGMP), (1,2). All on the
same 253
CLINICAL
TABLE Clinical
AND
RESEARCH
Am
REPORTS
J Psychiatry
of CSF cAMP
in 20 Schizophrenic
“Indicator N=20
variable”
in the case of noncontinuous
.54 .52 .47 -.45 .50
poor)
or affective
blunting),
speed
of first
re-
mission (quick, moderate, or slow), number of past hospitalizations, number of months between hospitalizations, quality of intermorbid adjustment (good, moderate, poor), total number of years ill, and severity of present illness at the time of spinal tap. Correlational analysis and multiple regression were done by the central computer at the Tel Aviv University. Results
Table 1 shows the five variables that were significantly correlated with CSF cAMP. Diagnosis of simple schizophrenia, slow first remission, poor intermorbid adjustment, young age of onset, and absence of hallucinations ing CSF
are all significantly cAMP. CSF cGMP
Regression
Variables
p< .01 p
J Psychiatry
135:2,
chotic medication family history her movement her prescribed phenidate in symptoms
of
methapyrilene methylphenidate,
She
had
February
1978
CLINICAL
and lithium. There was no personal or of neurologic disease. At least 2 weeks before disorder developed, she had stopped taking medication and had begun to abuse methyldoses of 30-100 mg/day. After developing movement disorder, she had started taking in doses of up to 250 mg/day in addition to the without changes in her symptoms.
marked
choreoathetosis
of all extremities,
responsive to halopenidol, a blocker mine receptors, are consistent with mine hypothesis.
head,
The
have
recurrence
The
pathophysiology and
to involve in the
and
increased
brain
the
(1).
Stimulants
activity, disorders
in hyperkinetic
Clinical
A recent
been
tentiates
such
as
have and
been reported dyskinesias
children
(3). These
of CSF
study
reported
that
mean
are
Nucleotides
BIEDERMAN,
cAMP
values
schizophrenic ues were prognoses
was
significantly
cyclic
greater
in
M.D.,
RANAN
among
sig-
of schizophrenic
ciated
with
poor-prognosis
patients
with
process
high cAMP, schizophrenia.
from
the Scottish
0002-953X/78/0002-0253$0.40
RIMON,
of has
cholinergic
activity.
75:203-212,
1972
M.D.,
The missions rusalem
assoThe
Rite Schizo-
was
period
patient
EBSTEIN,
designed
group
PH.D.,
to systematically
consisted
of drug-free Mental Health
of December
diagnosis trists (1).
evaluate
was No
made patient
of 20 consecutive
ad-
schizophrenic patients Center inpatient unit
to the during
1975
1976.
through
by consensus had received
August oftwo staff neuroleptic
Jethe
The
psychiatreat-
ment for at least 2 weeks prior to admission. Of the 20 patients, 19 had been hospitalized previously and 2 had a 2-year history of illness before his first hospitalization. viously
CSF biochemical data for 10 of the 20 patients
Lumbar CSF was obtained cAMP and cyclic guanosine were measured as described sample
© 1978
RICHARD
Method
the
When this work was done, Drs. Zohar and Biederman were Residents in Psychiatry and Dr. Rimon was Visiting Professor, Jerusa1cm Mental Health Center, Ezrath Nashim, where Dr. Ebstein is Senior Biochemist and Dr. Belmaker is Director of Research. Address reprint requests to Dr. Belmaker at P.O. Box 140, Jerusalem Mental Health Center, Ezrath Nashim, Jerusalem, Israel. This work was supported by a grant phrenia Research Program.
use
Schizophrenia
the
patients, and the two highest cAMP valin schizophrenic patients with notably poor (1). This suggested the existence of a sub-
group
to the influence
HL, Weiner WI: The pharmacology of choreatic disorders. Prog Neurobiol 6:49-80, 1976 0: Psychoses and the punding and choreiform synaddiction to central stimulant drugs. Psychiatr Neurol
present study this hypothesis.
adenosinc
monophosphate (cAMP) levels in the ccrcbnospinal fluid (CSF) of schizophrenic patients do not differ nificantly from those of pneanesthctic psychiatrically normal controls (1). However, the variance of
related
cholinergic
of there
Denckla MB, Bemporad JR. McKay MC: Tics following methylphenidate administration. JAMA 235: 1349-135 1 , 1976 4. Klawans HL, Weiner WJ: The effect of d-amphetamine on choreiform movement disorders. Neurology 24:312-318, 1974 5. Thack IT, Chase TN, Bosma IF: Oral facial dyskinesia associated with prolonged use of antihistaminic decongestants. N EngI J Med 293:486-487, 1975
to (2)
stimulants
antihistaminic/anti-
3.
do-
to lead addicts
dopadopa-
in the development be noted since
of dyskinesias
central
Neurochir
influence
in
Cyclic
ZOHAR, M.D., JOSEPH H. BELMAKER, M.D.
dis-
central
the
Decreased
(5).
1 . Klawans movement 2. Rylander dromes in
methylphenidatc
potentiate
of
of central the above
REFERENCES
hypothesized
neuronal
which
Correlates
BY JOSEPH AND ROBERT
movement
has
dopaminergic
amphetamines,
paminengic chorciform
and
dyskinesias
reports
drugs
of her symptoms.
of chorciform
related
REPORTS
been hypothesized to play a role in choreiform movement disorders (1); however, this patient showed no improvement following physostigmine, a drug that po-
Discussion
orders
role
drug methapyrilene symptoms should
been
these
was then given haloperidol, 4 mg I.M. over 60 minutes. She went to sleep briefly and awoke markedly improved, with only a mild residual movement disorder. She was instructed to take low doses of oral haloperidol for several days. At 1-
she denied
possible
cholinergic this patient’s
She was given physostigmine, 3 mg I.M. over 90 minutes. There was no improvement. and she became nauseated. She
follow-up
RESEARCH
known to exacerbate the symptoms of chorea (4), while dopamine-blocking drugs are known to improve chorciform symptoms (1). The findings in this patient of a choreiform syndrome that was precipitated by methylphenidate, a potentiator of dopamine, and was
and neck, as well as buccal-facial-lingual dyskinesias. The physical exam, which included a neurologic assessment, was otherwise unremarkable except for dry mouth, tachycardia, and sluggish mid-position pupils. She was alert. oriented, and mildly hypomanic. Routine laboratory tests were unremarkable.
month
AND
American
assays Psychiatric
were
done Association
had been (1).
and cyclic monophosphate previously
in a single
batch
reported
pre-
nucleotides, (cGMP), (1,2). All on the
same 253
CLINICAL
TABLE Clinical
AND
RESEARCH
Am
REPORTS
J Psychiatry
of CSF cAMP
in 20 Schizophrenic
“Indicator N=20
variable”
in the case of noncontinuous
.54 .52 .47 -.45 .50
poor)
or affective
blunting),
speed
of first
re-
mission (quick, moderate, or slow), number of past hospitalizations, number of months between hospitalizations, quality of intermorbid adjustment (good, moderate, poor), total number of years ill, and severity of present illness at the time of spinal tap. Correlational analysis and multiple regression were done by the central computer at the Tel Aviv University. Results
Table 1 shows the five variables that were significantly correlated with CSF cAMP. Diagnosis of simple schizophrenia, slow first remission, poor intermorbid adjustment, young age of onset, and absence of hallucinations ing CSF
are all significantly cAMP. CSF cGMP
Regression
Variables
p< .01 p
