AMINO
ACIDS
IN
BIPOLAR
ILLNESS
Amino
Acids
Levels
in Erythrocytes
BY
SEYMOUR
JESSE
Am
in Bipolar
ROSENBLATT,
S. ROSENTHAL,
Affective
M.D.,
M.D.,
GERALD
HARRY
Disorders:
E.
SMITH,
GAULL,
PH.D.,
A
NUMBER
abnormalities
OF
erythrocytes
of
activity (COMT),
with
of erythrocyte an important
tabolism,
has
have
patients
been
been
reported
affective
catechol enzyme reported
by
some,
but
not
depressive
in-
vestigators to be different in patients with primary affective disorders than in normal control groups (1). The biochemical properties of the emythrocyte enzyme indicate that it is probably identical to brain COMT (2).
The
erythrocyte
also
contains
an
active
cation
system similar to that of the neuron with affective illness there is a decrease
transport
patients activities
of
sensitive with the
the
erythrocyte
Na,K-ATPase administration
activity
may
Na
pump
and
(3). In in the ouabain-
(4). Both are stimulated of lithium, and the increase
be related
to the
improvement
in
of depres-
sive states and the prophylactic efficacy of lithium maintenance therapy (5). The erythrocyte, therefore, is a useful cellular mod-
Received
Aug.
8,
1978;
revised
Dec.
18,
1978;
accepted
Ian.
10,
1979. Dr. Rosenblatt is Associate Clinical Professor of Psychiatry and Chiefofthe Affective Disorders Clinic, and Dr. Rosenthal is Clinical Instructor of Psychiatry, Department of Psychiatry, Mt. Sinai School of Medicine, Annenberg 22, New York, N.Y. 10029, where Dr. Gaull is Professor of Pediatrics, Department of Pediatrics, Dr. Chanley is Professor of Biochemistry, Department of Biochemistry, Dr. Smith is Chairman, Department of Biostatistics, and Dr. Sarkozi is Director, Department of Chemistry, and Associate Professor of Clinical Pathology.
This
work
was
supported
in part
by the lack
Mack Foundation and National Institutes the Division of Research Resources. The
authors
assistance in whose 672
wish
to thank
and Dr. Marian laboratory several
Mrs.
Orlowski, ofthese
Nevenda
Martin
of Health
Vuckovic
Department determinations
0002-953X/79/06/0672/03/$00.40
Fund
and the RR-71 from
grant
for
CHANLEY.
some affective
PH.D.,
PH.D.
of the disorders.
physiological Because
chanacamino
acid
patients
were
examined.
METHOD
meall,
ofthe
1979
transport also is under the control ofan active, energydependent carrier system (6), the concentrations of amino acids in the enythnocytes and plasma of manic-
The
O-methyltransferase in biogenic amine
D.
136:5, May
Glycine
SARKOZI,
investigating
teristics
in the
illnesses.
JACOB
LASZLO
el for
The authors measured the concentrations of2O amino acids in the erythrocytes andplasma ofl3female bipolarpatients and lOfemale normal controls. The concentration ofg!vcine in the erythrocyte was significantly elevated in the patient group. No differences were present in the plasma. Preliminary findings indicate that the high glvcine levels were present in patients svho st’ere depressed, manic, or in remission and s’ere unaffected by electroshock therapy.
Increased
M.D.,
AND
J Psychiatry
laboratory
of Pharmacology, were replicated. © 1979
The patients consisted of 13 women, 33-72 years old, who had affective illnesses of 10 to 20 years in duration. Ten were bipolar manic-depressives, and 3 were considered to have schizo-affective illness because of their psychopathology during acute episodes. However, because there were no residual symptoms, decrement in functioning, or personality deterioration after remission from multiple acute phases of illness, a diagnosis of manic-depression could be equally valid. The control group consisted of 10 female hospital pensonnel, aged 24-58 years, without personal or family history of an affective illness. They were in good health and not on any medication. Neither group was taking oral contraceptives. Six patients and 8 controls were premenopausal, and 7 patients and 2 controls were in menopause. Of the 10 bipolar patients 3 were in remission and receiving 600 mg/day of lithium carbonate. These patients had not had an affective illness for at least 1 year, were in good health, and were not hospitalized for this study. Lithium carbonate was stopped for 7 days in these patients before blood was taken for amino acid analysis. Of the 10 hospitalized patients, 8 were depressed. Prior to admission they were under treatment with inadequate dosages of tnicyclic antidepressants and had not been on maintenance lithium carbonate therapy. Two of the hospitalized patients were in the manic phase ofthein illness. At the time of hospitalization, all medication was discontinued for the depressed patients but was not interrupted for the 2 manic patients, 1 of whom ium carbonate (1200 mg/day)
continued and the
(10 mg/day).
underwent
ical
All
examinations
13 patients and
complete
to receive lithother halopenidol
blood
routine and
phys-
laboratory
studies. Except for 1 patient, a known diabetic, all of the findings were within normal limits. The diabetic patient had an elevated fasting blood glucose of 180 mg/lOO
American
cc
but
was
Psychiatric
not
excreting
Association
ketone
bodies.
This
A,n
J Psychiatry
patient
136:5,
was
placed
additional
on
insulin,
control.
Dietary
patients (Sustecal).
by
May
/979
ROSENBLATT,
a 1 ,200-calorie
which
brought
control
was
than 2,000 calories. regimen in addition before blood was
after structed tamed
an overnight to that
and
diabetes
maintained
the use of liquid The patients drank
given under
in the
nutritional 12 ounces than 50%
ment whenever they ate less The daily caloric intake of these less tary days
diet the
was
never
The patients were on the dieto being drug-free for at least 5 drawn for amino acid analysis
fast.
The
control
subjects
were
adhere to their usual diets. It was they were on conventional balanced
none was on a weight reduction Blood (15 cc) was drawn into
in-
ascerdiets:
acid
determined
with
autoanalyzer
(7).
an automated
of Erythrocyte
Glycine
E
I
higher in the (56.3 molJl00 (p-i
a
0 Li
20
Li
10 0
Patients
was
I 20
I 30 Premenopause
equations:
,
in serine
,
valine,
leucine,
,
isoleucine,
anine, ornithine, lysine, histidine, glutathione. Erythrocyte glycine concentrations, strual status are shown in figure
present cine
between levels
of
the the
patient patients
and were
tyrosine,
phenylal-
methionine, ages, and 1 . No overlap
control
values.
significantly
and menwas
Glyhigher
than those of the controls as shown by parallel prediction equations. Glycine levels decreased with age. The slope of glycine versus age was -0.2456 for the controls and -0.4530 for the patients, and a t test for diffenence between the two slopes was not significant (t=.92, p
ACIDS
IN
BIPOLAR
ILLNESS
Amino
Acids
Levels
in Erythrocytes
BY
SEYMOUR
JESSE
Am
in Bipolar
ROSENBLATT,
S. ROSENTHAL,
Affective
M.D.,
M.D.,
GERALD
HARRY
Disorders:
E.
SMITH,
GAULL,
PH.D.,
A
NUMBER
abnormalities
OF
erythrocytes
of
activity (COMT),
with
of erythrocyte an important
tabolism,
has
have
patients
been
been
reported
affective
catechol enzyme reported
by
some,
but
not
depressive
in-
vestigators to be different in patients with primary affective disorders than in normal control groups (1). The biochemical properties of the emythrocyte enzyme indicate that it is probably identical to brain COMT (2).
The
erythrocyte
also
contains
an
active
cation
system similar to that of the neuron with affective illness there is a decrease
transport
patients activities
of
sensitive with the
the
erythrocyte
Na,K-ATPase administration
activity
may
Na
pump
and
(3). In in the ouabain-
(4). Both are stimulated of lithium, and the increase
be related
to the
improvement
in
of depres-
sive states and the prophylactic efficacy of lithium maintenance therapy (5). The erythrocyte, therefore, is a useful cellular mod-
Received
Aug.
8,
1978;
revised
Dec.
18,
1978;
accepted
Ian.
10,
1979. Dr. Rosenblatt is Associate Clinical Professor of Psychiatry and Chiefofthe Affective Disorders Clinic, and Dr. Rosenthal is Clinical Instructor of Psychiatry, Department of Psychiatry, Mt. Sinai School of Medicine, Annenberg 22, New York, N.Y. 10029, where Dr. Gaull is Professor of Pediatrics, Department of Pediatrics, Dr. Chanley is Professor of Biochemistry, Department of Biochemistry, Dr. Smith is Chairman, Department of Biostatistics, and Dr. Sarkozi is Director, Department of Chemistry, and Associate Professor of Clinical Pathology.
This
work
was
supported
in part
by the lack
Mack Foundation and National Institutes the Division of Research Resources. The
authors
assistance in whose 672
wish
to thank
and Dr. Marian laboratory several
Mrs.
Orlowski, ofthese
Nevenda
Martin
of Health
Vuckovic
Department determinations
0002-953X/79/06/0672/03/$00.40
Fund
and the RR-71 from
grant
for
CHANLEY.
some affective
PH.D.,
PH.D.
of the disorders.
physiological Because
chanacamino
acid
patients
were
examined.
METHOD
meall,
ofthe
1979
transport also is under the control ofan active, energydependent carrier system (6), the concentrations of amino acids in the enythnocytes and plasma of manic-
The
O-methyltransferase in biogenic amine
D.
136:5, May
Glycine
SARKOZI,
investigating
teristics
in the
illnesses.
JACOB
LASZLO
el for
The authors measured the concentrations of2O amino acids in the erythrocytes andplasma ofl3female bipolarpatients and lOfemale normal controls. The concentration ofg!vcine in the erythrocyte was significantly elevated in the patient group. No differences were present in the plasma. Preliminary findings indicate that the high glvcine levels were present in patients svho st’ere depressed, manic, or in remission and s’ere unaffected by electroshock therapy.
Increased
M.D.,
AND
J Psychiatry
laboratory
of Pharmacology, were replicated. © 1979
The patients consisted of 13 women, 33-72 years old, who had affective illnesses of 10 to 20 years in duration. Ten were bipolar manic-depressives, and 3 were considered to have schizo-affective illness because of their psychopathology during acute episodes. However, because there were no residual symptoms, decrement in functioning, or personality deterioration after remission from multiple acute phases of illness, a diagnosis of manic-depression could be equally valid. The control group consisted of 10 female hospital pensonnel, aged 24-58 years, without personal or family history of an affective illness. They were in good health and not on any medication. Neither group was taking oral contraceptives. Six patients and 8 controls were premenopausal, and 7 patients and 2 controls were in menopause. Of the 10 bipolar patients 3 were in remission and receiving 600 mg/day of lithium carbonate. These patients had not had an affective illness for at least 1 year, were in good health, and were not hospitalized for this study. Lithium carbonate was stopped for 7 days in these patients before blood was taken for amino acid analysis. Of the 10 hospitalized patients, 8 were depressed. Prior to admission they were under treatment with inadequate dosages of tnicyclic antidepressants and had not been on maintenance lithium carbonate therapy. Two of the hospitalized patients were in the manic phase ofthein illness. At the time of hospitalization, all medication was discontinued for the depressed patients but was not interrupted for the 2 manic patients, 1 of whom ium carbonate (1200 mg/day)
continued and the
(10 mg/day).
underwent
ical
All
examinations
13 patients and
complete
to receive lithother halopenidol
blood
routine and
phys-
laboratory
studies. Except for 1 patient, a known diabetic, all of the findings were within normal limits. The diabetic patient had an elevated fasting blood glucose of 180 mg/lOO
American
cc
but
was
Psychiatric
not
excreting
Association
ketone
bodies.
This
A,n
J Psychiatry
patient
136:5,
was
placed
additional
on
insulin,
control.
Dietary
patients (Sustecal).
by
May
/979
ROSENBLATT,
a 1 ,200-calorie
which
brought
control
was
than 2,000 calories. regimen in addition before blood was
after structed tamed
an overnight to that
and
diabetes
maintained
the use of liquid The patients drank
given under
in the
nutritional 12 ounces than 50%
ment whenever they ate less The daily caloric intake of these less tary days
diet the
was
never
The patients were on the dieto being drug-free for at least 5 drawn for amino acid analysis
fast.
The
control
subjects
were
adhere to their usual diets. It was they were on conventional balanced
none was on a weight reduction Blood (15 cc) was drawn into
in-
ascerdiets:
acid
determined
with
autoanalyzer
(7).
an automated
of Erythrocyte
Glycine
E
I
higher in the (56.3 molJl00 (p-i
a
0 Li
20
Li
10 0
Patients
was
I 20
I 30 Premenopause
equations:
,
in serine
,
valine,
leucine,
,
isoleucine,
anine, ornithine, lysine, histidine, glutathione. Erythrocyte glycine concentrations, strual status are shown in figure
present cine
between levels
of
the the
patient patients
and were
tyrosine,
phenylal-
methionine, ages, and 1 . No overlap
control
values.
significantly
and menwas
Glyhigher
than those of the controls as shown by parallel prediction equations. Glycine levels decreased with age. The slope of glycine versus age was -0.2456 for the controls and -0.4530 for the patients, and a t test for diffenence between the two slopes was not significant (t=.92, p
