CATECHOLAMINE EXCRETION IN MANIC.

DEPRESSIVE AND
SCHIZOPHRENIC PSYCHOSIS AND ITS RELATIONSHIP
TO SYMPTOMATOLOGY*
R. B. SLOANE, M.D.', W. HUGHES, M.B:, AND H. L. HAUST, M.D., PH.D:

Introduction in the depressed state, noradrenalin was

There are a number of studies suggest- excreted preferentially as compared to
ing that the urinary excretion of cate- adrenalin and corticoids, whilst the lat-
cholamines is increased where anxiety or ter were excreted preferentially in states
tension is present. Nilsson (17), for of anxiety. In subjects whose principal
example, found a correlation between difficulties lie in disorders of thinking or
tension and restlessness and adrenalin behaviour, there was a preferential ex-
excretion in females (but not males). cretion of adrenalin or noradrenalin.
Levi in a series of studies (14,15,16) However, none of these findings were
showed that the excretion of both adren- significant, and it was only when
alin and noradrenalin was increased adrenalin, noradrenalin and 17~hy­
under experimental stress and that this droxycorticosteroids were considered to-
seemed independent of emotional vulner- gether that a significant variance between
ability. Sloane et at. (22) noted a positive affect and hormonal excretion was
correlation between the Taylor Manifest achieved.
Anxiety Scale and excretion of adrenalin Bergsman (2) found an elevated ex-
in normal subjects under stress. Sourkes cretion of both adrenalin and noradren-
et at. (23) found that the higher the alin during the manic phase of manic-
catecholamine excretion rate, the worse depressive psychosis and an increased
the prognosis is with KeT. This would excretion in manic patients in general
be in accord with the clinical notion of a compared to those suffering from depres-
poorer response to this therapy in the sion.
presence of anxiety.
On the basis of the structural re-
Bunney (4) reported that the anxiety, semblance of methylated catecholamine
anger or depression, frequently accentu- derivatives to the hallucinogenic, mesca-
ated in depressively ill patients as the line, Osmond and Smythies (18) impli-
result of the stress of admission to hos- cated aberrant catecholamine metabolism
pital, were accompanied by an increased in the development of schizophrenia.
output of catecholamines. Although such a theory is intriguing, no
From studies on the excretion patterns confirmatory evidence has yet been
of both catecholamines and 17-hydroxy- forthcoming. Indeed, presently available
corticosteroids in anxious or depressed information would seem to indicate that
patients, Curtis et at. (8) concluded that there is no difference in the metabolism
"This study is part of a project carried out with the of adrenalin, both endogenous and exo-
assistance of a Canadian Dominion-Provincial Mental
Health Grant (Project No. 605-5-282). genous, between schizophrenic patients
Revision of paper presented at the Annual Meeting
of the Canadian Psychiatric Association, June, 1964, and normal controls (2,6,13,20,21).
Vancouver.
From the departments of psychiatry and biochem- Such conflicting and fragmentary evi-
istry, Queen's University, Kingston, Ontario:
'Professor and Chairman, Department of Psychiatry, dence for any clear-cut or consistent
Temple University Medical Center, Philadelphia; form-
erly Professor and Head, Department of Psychiatry, relationship between patterns of cate-
Queen's University.
'Psychiatrist in Charge, York County Hospital, New-
cholamine excretion on one hand and the
market, Ontario.
Assistant Professor, Department of Biochemistry,
affective state and psychotic illness on
the other, prompted the investigation to
S
Queen's University; presently Visiting Scientist, Na-
tional Heart Institute, National Institutes of Health,
Bethesda, Maryland. be reported in this publication.
6
February, 1966 CATECHOLAMINE EXCRETION IN PSYCHOSES 7

TABLE I
AGES OF PATIENTS

Diagnosis Number Mean age Standard Deviation

Schizophrenic reaction 38 36.34 ±18.04
years
Manic-depressive reaction, 39 47.86 ±11.10
depressed years
Manic-depressive reaction, 7 52.42 ±12.83
manic years

F ratio = 12.88
sig. at beyond .01 level
t Tests
Between manic-depressive depressed and manic-depressive manic 1.16
Between manic-depressive depressed and schizophrenic 4.20**
Between manic-depressive manic and schizophrenic 4.11 **
** = sig. at beyond .01 level
Schizophrenics sig. younger than affective groups. No difference between manic-depressive depressed
and manic.

This study set out to discover whether
there were differences in the urinary
excretion of adrenalin, noradrenalin
and dopamine in schizophrenic and
manic-depressive psychotic patients be-
tween their 'sick' and 'well' phases. In this
way, each patient served as his own con-
trol. In addition, and probably with less
validity, this study permitted the es-
tablishment of trends, if any, in catechol-
amine excretion in relation to diagnosis.
Because of the known lack of reliability
in psychiatric diagnosis, ratings of a
variety of symptoms, including anxiety
and depression, and of somatic (mus-
culoskeletal) and visceral (autonomic)
complaints were carried out.
Method
All patients admitted to the Ontario
Hospital, Kingston, with a diagnosis of
either schizophrenia or manic-depressive
psychosis during the course of the in-
vestigation, were studied. They were
excluded only if there were organic brain
disease, significant physical illness or
mental deficiency.
A total of 84 subjects included on ad-
mission to hospital fell into one of the
following three diagnostic groups:
schizophrenic reaction (undifferentiated
type) ; manic-depressive reaction, de-
pressed; manic-depressive reaction, ma-
nic. The number of cases and mean ages
per group are shown in Table I. It will
be noted that the schizophrenic patients
were significantly younger than the
manic-depressive ones.
Procedure
1) Interview and rating
The patients were seen as soon as pos-
sible after admission by one psychiatrist
(WH). The following rating scales were
then completed:
a) A general mental status scale"
b) The Taylor Manifest Anxiety
Scale (TMAS) (27)
c) A check list of physical symp-
toms" (5)
i) somatic musculoskeletal
ii) autonomic visceral
d) The Inglis Depression Rating Scale
(11)
The questionnaire was read to the
patients by the examiner who recorded
the answers. This procedure was adopted
for the sake of uniformity, as some
patients were too ill on admission to com-
plete the scale themselves in the usual
way.
°Copies of these rating scales can be made available
to interested readers. .
8 CANADIAN PSYCHIATRIC ASSOCIATION JOURNAL
2) Treatment
Phenothiazines (usually chlorprom-
azine or thioridazine in varying doses)
were the usual treatment of the schizo-
phrenic and manic patients. Imipramine,
in some cases with electroconvulsive
therapy, was the treatment for those with
depression or the depressive phase of
mania.
3) Diagnosis
The final diagnosis was made by
agreement between the two psychiatrists
(W.H. and R.B.S.) at the time of the
patient's discharge, taking all available
clinical evidence into account. At this
time, the results of the catecholamine
determinations were not available.
4) Estimation of urinary catechol-
amines and creatinine
A 24-hour specimen of urine was col-
lected from each patient beginning at
midnight, within three days of admission.
A similar specimen was obtained in the
week before the patient's discharge from
hospital. Phenothiazine and antidepres-
sant medication was omitted for 48 hours
before collection. Interviewing was car-
ried out on the same day as urine was
obtained.
All urinary specimens were collected
over 20 ml. of 6N hydrochloric acid in
brown bottles provided with non-metallic
screw caps. Immediately upon receipt,
the entire collection was thoroughly
mixed, its acidity determined and ad-
justed to pH2, if necessary, and its
volume recorded. Representative amounts
of acid urine that could not be imme-
diately processed were stored in a deep
freezer in neoprene bottles.
Free catecholamines present in unhy-
drolyzed urine were determined by a
modification of the differential-spectro-
photofluorometric procedure of Sourkes
and Murphy (24) using an Aminco-
Bowman spectrophotofluorometer. All of
urinary aliquots, standard amounts of
catecholamine and blanks were carried
Vol. 11, No. 1
through adsorption on alumina and elu-
tion with each series of determinations,
thus obviating corrections for loss of
amine during the adsorption step. Re-
coveries of known amounts of the three
amines added to unpooled urine were as
follows: adrenalin, 96.8% -I- 11.2%
(SO); noradrenalin, 95.1% -I- 10.8%;
dopamine, 92.2% -I- 11.4%.
For creatinine determinations, dilutions
of 1:25, 1:50, and 1:00 were prepared
from a filtered portion of urine. One-
millilitre aliquots of each dilution were
subjected to an adaptation of the proce-
dure of Owen et al. (19). The chromo-
gen produced after the addition of alka-
line picrate was measured at 5200 A in
a. Coleman Junior spectrophotometer.
FIve standard concentrations of creati-
ni?~ .ranging ~rom 0.1 to 0.5 mg. per
millilitre were included in each series of
determinations. The amount of creatinine
present in anyone urinary sample was
computed from its concentrations in the
three dilutions. The values so obtained
agreed within 4.5 per cent (SO) of the
mean.
Although determination of urinary
creatinine served primarily as an alterna-
tive basis for expressing catecholamine
excretion, the values were found to be
themselves reduced significantly in the
group of manic-depressive depressed
patients on admission to hospital.
Results
It can be seen in Table II that the ex-
cretion of dopamine in manic patients
greatly exceeds (P is less than 0.01) that
of other patients both on admission and
discharge from hospital, whether ex-
pressed in absolute values or per gram of
creatinine. The significant variations in
ratio of excretion of dopamine to
adrenalin and noradrenalin in manic
patients shown in Table III merely re-
flect this raised output.
Neither adrenalin nor noradrenalin
show differential excretion between
diagnostic groups on admission to hospi-
tal.
 ""1
[
~
TABLE II
-
&
MEAN 24-HoUR URINARY OUTPUT OF CATECHOLAMINES AND OF CREATININE BY DIAGNOSIS
On Admission to Hospital

Schizophrenic Manic-depressive, Manic-depressive, F Ratio P

depressed manic
Number of Cases* 38 39 7
Mean 24-hour urine volume (ml) 846 726 762 0.59 NS o
~
Creatinine (grams) 1.05 0.79 1.00 3.31 <0.05
Catecholamines (micrograms) ~
Adrenalin 34. 1 ( 35.2 )** 26.9 ( 35.1) 35.9 ( 42.3) 1.6 (0.48) NS (NS) Z
Noradrenalin 52.6 ( 51.0) 41.1 ( 55.3) 67.8 ( 65.5) 1.5 (0.64) NS (NS) t'1
Dopamine 199.0 (209.0) 185.0 (242.0) 344.0 (605.0) 6.3 (6.60) <0.01 «0.01)
~
~
On Discharge from Hospital ~
~
Number of Cases" 27 31 5
Mean 24-hour urine volume (ml) 1,155 1,265 1,554 1.03 NS Z
Creatinine (grams) 1.16 1.14 1.21 0.06 NS 'd
Catecholamines (micrograms)
Adrenalin 41.6 ( 41.4)** 36.5 ( 34.9) 35.7 ( 34.9) 0.6 (0.93) NS (NS)
Noradrenalin 41.6 ( 40.2) 57.2 ( 57.0) 55.4 ( 68.9) 2.3 (2.10) NS (NS)
~o
(J)
Dopamine 193.0 (179.0) 212.0 (206.0) 495.0 (419.0) 6.0 (8.50) < 0.01 «0.01)
~

*Some patients were lost from the study for a variety of reasons.
**All data given in parentheses refer to, and in the case of the F-ratios and P values are derived from, the amount of catecholamines in micrograms excreted
per gram of creatinine. The output of creatinine in a given patient served as the denominator in the latter ratio, from which the mean values per diag-
nostic group on admission or discharge listed in parentheses were computed.

'0
 o

TABLE III
URINARY CATECHOLAMINES EXPRESSED AS RATIOS OF EACH OTHER BY DIAGNOSTIC GROUPS
On admission to hospital

Schizophrenic Manic-depressive,
depressed
Manic-depressive,
mamc F ratio P
I
Number of cases 38 39 7
Noradrenalin/Adrenalin 1.63 1.59 1.88 1.53 NS
~g
Dopamine/Adrenalin 7.14 8.17 14.65 3.78 <0.05 C')
Dopamine/Noradrenalin 5.07 6.12 4.97 0.93 NS
&;
en
g
On discharge from hospital

Number of cases 27 31 5 ~
Noradrenalin/Adrenalin 1.07 1.66 1. 70 4.6 <0.05
Dopamine/Adrenalin 4.15 6.31 11.36 6.2 <0.01
Dopamine/Noradrenalin 5.53 4.38 8.75 5.7 <0.01

1
<:
{2.
r-
-
~
 TABLE IV
A COMPARISON OF THE MEAN 24-HoUR OUTPUT OF CATECHOLAMINES IN THE URINE
FOR EACH DIAGNOSTIC GROUP ON ADMISSION AND DISCHARGE*
i9
SCHIZOPHRENIC ~
Number of cases 27
Admission A p
Discharge
Catecholamines (micrograms) (micrograms) ~
Adrenalin 37.2 ( 37.6)** 41.6 ( 42.9) 2.27 ( 1.20) NS (NS) ;;l
Noradrenalin 56.3 ( 51.5) 41.6 ( 40.2) 0.54 ( 0.51) NS (NS) o
Dopamine 200.0 (199.0) 193.0 (179.0) 1.26 ( 0.69) NS (NS)

MANIC-DEPRESSIVE, DEPRESSED I
Number of cases 31 ~
Admission Discharge A P
~
&l
Ca techolamines (micrograms) (microrams)
Adrenalin 25.9 ( 31.0) 36.5 34.9) 0.14 ( 0.45) <0.01 (NS)
Noradrenalin 37.7 ( 46.4) 57.2 ( 57.0) 0.14( 0.34) <0.01 (NS)
Dopamine 179.0 (214.0) 212.0 (206.0) 0.56 ( 2.80) NS (NS)
iz
'd

MANIC-DEPRESSIVE, MANIC :<

Number of cases 5
so
en
Admission A p ~
Discharge
Catecholamines (microframs) (micrograms)
Adrenalin 24.8 43.3) 35.7 ( 34.9) 1.31 ( 1.30) NS (NS)
Noradrenalin 62.0 ( 70.8) 55.4 ( 68.9) 20.00 (44.0) NS (NS)
Dopamine 249.0 (682.0) 495.0 (419.0) 1.30 (2.9) NS (NS)

*Only those patients whose urine was obtained on both admission and discharge are included.
**AII data given in parentheses refer to, and in the case of the A and P values are derived from, the amount of catecholamine in micrograms excreted per
gram of creatinine.
........
 ...
N

TABLE V
A COMPARISON OF THE MEAN 24-HoUR OUTPUT OF URINE AND OF CREATININE FOR EACH
DIAGNOSTIC GROUP ON ADMISSION AND DISCHARGE

SCHIZOPHRENIC

Number of cases 27
Admission Discharge A P
z
Volume (m1/24 hrs.) 1,133 1,155 820 NS
I
"C
Creatinine (g/24 hrs.) 1.12 1.16 100.0 NS ~
o
:xl
MANIC-DEPRESSIVE, DEPRESSED

Number of cases 31
Admission Discharge P
i
~
en
A
Volume (m1/24 hrs.) 700 1,265 0.03 <0.001
Creatinine (g/24 hrs.) 0.84 1.14 0.15 <0.01

MANIC-DEPRESSIVE, MANIC
ig
N umber of cases 5 I ~
>
t'"
Admission Discharge A P
Volume (m1/24 hrs.) 549 1,554 0.455 NS
Creatinine (g/24 hrs.) 0.77 1.21 0.74 NS

~...
...
...~
february, 1966 CATECHOLAMINE EXCRETION IN PSYCHOSES
The excretion of both adrenalin and
noradrenalin in depressed patients is
significantly less (P is less than 0.01) on
admission to hospital than on discharge.
This difference disappears when cate-
cholamines are expressed per gram of
creatinine excreted. Both urinary volume
and creatinine of the depressed group
on admission are seen to be also signifi-
cantly reduced, with the value for the
latter compound (P is less than 0.05)
lower than in schizophrenia or mania at
any stage (d. Tables II and V).
An inspection of Table VI reveals that
the schizophrenic patients on admission
have a significantly lower ratio of excre-
tion of adrenalin to noradrenalin, and
also a higher ratio of dopamine to adren-
alin, than on discharge.
A comparison between catecholamine
output and the various ratings, especially
those of thought disorder, fails to reveal
any significant correlations as far as the
schizophrenic group is concerned.
No significant correlation between
ratings of anxiety and catecholamine ex-
cretion is found when the patients are
grouped irrespective of diagnosis.
In the depressed patients (d. Table
VII) there is a significant relationship
between the excretion of dopamine and
manifest anxiety as shown in both the
anxiety rating scale and the TMAS.
Furthermore, significant relationships are
revealed, on one hand, between the de-
gree of manifest anxiety rated by the
psychiatrist and the excretion of adrenal-
in and noradrenalin and, on the other,
between the degree of depression and
dopamine excretion. When these relation-
ships are examined on the basis of the
catecholamine output per gram of cre-
atinine, their significance disappears.
In the manic patients the excretion of
noradrenalin is positively correlated
with ratings of anxiety and bodily symp-
toms, but significantly so only in the
former (there were only seven patients).
The ratings of both somatic and auto-
nomic symptomatology showed negative
13
but insignificant correlations with the
output of all catecholamines.
Discussion
A striking finding in the present work
was the greatly increased output of
dopamine observed on both admission to
and discharge from hospital in the small
group of patients suffering from manic
disturbance. These data are remarkably
similar to results obtained by Strom-
Olsen and Weil-Malherbe (26). In addi-
tion to an increased output of dopamine
during the manic phase in one patient,
these workers noted a general tendency
towards an increased excretion of this
compound in mania. These findings,
which did not reach statistical signifi-
cance, were attributed to a renal origin,
since an increase of dopamine could not
be demonstrated in venous plasma.
However Sourkes (25) has compiled
evidence to indicate that experimentally
induced increases or decreases of cerebral
dopamine content may lead to stimula-
tion and depression, respectively, of be-
haviour. Furthermore, the conversion of
dopamine to noradrenalin has been
found by Goldstein and Contrera (10)
to be inhibited by pentobarbitone in
vitro. Barbeau and Sourkes (1) have
pointed out that increased concentrations
of dopamine in tissues may result not
only from a block in its conversion to
noradrenalin, but also from one of its
degradation to homovanillic acid, or may
ensue a priori from excess precursor
dopamine. Thus, if any such defect,
whether intrinsic to manic disturbance
or drug-induced, were general, so as to
include the liver and kidneys, urinary
concentrations of dopamine might be
expected to be high.
On the other hand, the possibility can-
not be overlooked that high values of
urinary dopamine in mania, which in the
present study reached levels up to 1,600
micrograms per 24 hours, may, in part at
least, be spurious and contributed to by
a compound other than dopamine but
indistinguishable from it by the analytical
 -...
TABLE VI
URINARY CATECHOLAMINES EXPRESSED AS RATIOS OF EACH OTHER FOR EACH
DIAGNOSTIC GROUP ON ADMISSION AND DISCHARGE

SCHIZOPHRENIC

N umber of cases 27
Admission Discharge A p

Noradrenalin/Adrenalin 1.60 1.07 0.17 <0.02

Dopamine/Adrenalin 6.38 4.15 0.06 <0.001 ' tl
Dopamine/Noradrenalin 4.60 5.53 1.12 NS
I
rn
@
MANIC-DEPRESSIVE, DEPRESSED

Number of cases 31
~
>-
Admission Discharge A p rn

Noradrenalin/Adrenalin 1.49 1.66 0.86 NS

Dopamine/Adrenalin 8.22 6.31 0.32 NS
Dopamine/Noradrenalin 6.12 4.38 0.35 NS

.....
MANIC-DEPRESSIVE, MANIC
I
Nnmber of cases 5
Admission Discharge A P
NS
i
Noradrenalin/Adrenalin 2.17 1.70 1.36
Dopamine/Adrenalin 16.80 11.36 4.90 NS
Dopamine/Noradrenalin 3.22 8.75 0.46 NS <:
~
....
r-
~
 TABLE VII
ic
~
CORRELATION COEFFICIENTS BETWEEN CATECHOLAMINE OUTPUT AND SYMPTOMS ':;<:
....
~
SCHIZOPHRENIC 0\

N Adrenalin Noradrenalin Dopamine

Thought Disorder 32 +0.01 ( +0.08)* -0.11 (-0.12) +0.14 (+0.15)
Anxiety Rating Scale 38 -0.04 ( -0.04) +0.06 (+0.13) +0.14 (+0.18)
Taylor Manifest Anxiety Scale 29 -0.24 (-0.16) -0.21 (-0.10) -0.14 (+0.02)
Somatic Symptom Rating Scale 30 -0.15 (-0.18) -0.15 ( -0.08) +0.04 (+0.00)
Autonomic Rating Scale 30 -0.16 (-0.13) -0.08 (-0.00) +0.11 (+0.11)
o
~
MANIC-DEPRESSIVE, DEPRESSED ~
Z
M
N Adrenalin Noradrenalin Dopamine ~
Anxiety Rating Scale 39 +0.53** (+0.10) +0.32*** (+0.26) +0.53** (+0.22) ~
Taylor Manifest Anxiety Scale 36 +0.09 (-0.17) +0.04 (-0.09) +0.55** (+0.32) ~
Somatic Symptom Rating Scale 36 -0.09 (-0.08) -0.08 (-0.17) -0.27 (-0.19)
Autonomic Rating Scale 38 -0.12 (-0.13) -0.05 (-0.25) -0.32 ( -0.20) ~
Inglis Depression Rating Scale 39 +0.14 (-0.20) +0.26 (-0.06) +0.55** (+0.24) Z
"d
MANIC-DEPRESSIVE, MANIC ~
Q
N Adrenalin Noradrenalin Dopamine
£
~
Anxiety Rating Scale 7 +0.66 (-0.11) +0.46 (+0.36) +0.15 (-0.43)
Taylor Manifest Anxiety Scale 6 +0.15 (+0.39) +0.75 (+0.93)** +0.01 ~-0.10)
Somatic Symptom Rating Scale 7 +0.21 (+0.07) +0.50 (+0.53) +0.60 -0.02)
Autonomic Rating Scale 7 +0.22 (+0.14) +0.39 (+0.41) +0.70 (+0.13)

*Data in parentheses are based upon catecholamine: creatinine ratios.

up is less than 0.01
***p is less than 0.05
....
'""
16 CANADIAN PSYCHIATRIC ASSOCIATION JOURNAL
criteria employed. (Whether or not such
a hypothetical compound is characteris-
tically excreted in mania cannot be ascer-
tained.)
The other interesting finding emerging
from the present work is the significant
reduction in the output of both adrenalin
and noradrenalin in the depressed
patients found on admission as compared
to discharge from hospital. These results
may be viewed in the light of data offered
by Bergsman (2). Although the latter in-
vestigator found no difference in the
excretion of both catecholamines be-
tween depressed and normal subjects at
rest, following insulin administration
there was a rise which in the case of the
depressed group was significantly lower
than that observed in either normal sub-
jects or in patients suffering from mania.
This may suggest failure of mobilization
due to depletion or exhaustion of
catecholamine reserves as a result of
antecedent prolonged oversecretion. In
fact, Bergsman's clinical protocols in-
dicate periodicity and probably chron-
icity of the patients chosen for investiga-
tion.
On the basis of the foregoing con-
siderations, the raised output of adrenal-
in and noradrenalin noted in the pre-
sent study for the group of depressed
patients at the time of their discharge
from hospital, may be taken as a reflec-
tion of the physiological recovery that
should accompany clinical improvement.
Although these changes may be attribut-
able to the possible continuing effect of
imipramine, it remains intriguing that the
degree of actual depression in this group,
as judged by the Inglis Depression Rating
Scale, was significantly correlated with
the amount of dopamine excreted. This
raises the possibility that during re-
covery of these patients from their illness,
more of this compound might have been
converted to noradrenalin and adrenalin
to account for the increased excretion of
the latter two amines when the patients
were discharged.
Vol. 11, No.1
Along with the raised output of
adrenalin and noradrenalin, urine
volume of these patients at this stage was
also significantly higher than on their
admission. This may be linked to data
offered by Strom-Olsen and Weil-
Malherbe (26) indicating, as do those of
Bergsman (2), that groups of patients
showing an increased excretion of the
two amines also reveal increased diuresis.
Pertinent, too, is recent work by Dawson
and Bone (9) in which these investigators
showed, by reanalysis of Strom-alsen's
and Weil-Malherbe's results and evalu-
ation of additional data of their own,
that the output of adrenalin and nor-
adrenalin was significantly correlated
with urine volume.
It is noteworthy that depressed patients
upon recovery from illness were found
by Coppen and Shaw (7) to have in-
creases in total body water along with
redistribution of sodium. Although the
relationship of these findings to depres-
sion remains to be elucidated, it may be
that they are reflected in the significant
increase in urine volume found in the
present study in comparable circum-
stances.
The significant reduction in the 24-
hour output of creatinine noted for the
depressed patients on admission to hospi-
tal deserves special comment. As indi-
cated earlier, determination of creatinine
was customarily included in the present
investigation to provide an alternative
basis for expressing catecholamine excre-
tion. This finding illustrates that such a
rationale may not be valid. There were
no known errors in the collection of
urine over a 24-hour period and those
that might have escaped detection seem
unlikely to have been confined to one
group at one stage of the investigation.
In view of the presence of preformed
creatinine in common food stuffs, such
as meat and fish, low values for creatinine
in the group of depressed patients at the
time of their admission may indicate that
these patients were eating less when they
February, 1966 CATECHOLAMINE EXCRETION IN PSYCHOSES
were sick. However, the possibility can-
not be excluded that this finding is
attributable to a hitherto unrecognized
metabolic defect in depression to which
these significantly reduce.d values for
adrenalin, noradrenalin and urine
volume may further attest. This possi-
bility should warrant further investiga-
tion. It may be pertinent to note that
Berlet and his colleagues (3) have re-
cently shown that the converse, viz.
creatininuria, is among the biochemical
phenomena accompanying episodes of
marked behavioural activation in schizo-
phrenia, and that during such episodes,
urinary volume may also be increased.
It should be noted that although the
mean age of the schizophrenic patients
in the present study was below that of
the two other groups, there were no
group differences as far as the catechola-
mine output was concerned. The impor-
tance, if any, of the altered ratios of the
excretion of adrenalin to noradrenalin
in the schizophrenic patients on admis-
sion, as well as the raised ratio of
dopamine to adrenalin on their dis-
charge, remains to be ascertained. The
lack of significant variation in cate-
cholamine excretion between the 'sick'
and 'recovered' phases of the illness,
along with the absence of any correlation
between catecholamine output and the
degree of thought disorder, are in line
with the data of Bergsman (2). Both find-
ings would, at this point, argue against
major disturbance of catecholamine meta-
bolism in schizophrenia. This conclusion
receives support from studies implying
that the fraction of catecholamine
metabolized to, and appearing in urine as
vanillyl-mandelic acid and metanephrine
reveals no major quantitative differences
between schizophrenic patients and nor-
mal controls (12). Thus, the hypothesis
of aberrant catecholamine metabolism in
schizophrenia advanced by Osmond and
Smythies (18) on the basis of structural
similarity of methylated derivatives to
the hallucinogenic, mescaline, remains
unconfirmed.
17
The Taylor Manifest Anxiety Scale
contains many items of bodily symptom-
atology and might be expected to cor-
relate in the way we found with the
ratings of somatic symptoms.
However, the lack of relationship
between visceral symptoms and cate-
cholamine excretion may indicate that
there is no necessary correlation between
these and circulating adrenalin or
merely that the small percentage esti-
mated in the urine as free catecholamine
is a poor indicator of the amount in the
body. The negative relationship between
estimates of overt anxiety and somatic
symptoms in general would be in keep-
ing with the idea that bodily symptoms
replace overt anxiety, although that does
not answer the question of the role of
amines in such symptoms.
Summary
In a group of depressed manic-depres-
sive patients, urinary adrenalin, nor-
adrenalin, creatinine and volume on
admission of the patients to hospital were
significantly reduced compared to the
values found on their discharge. A small
sample of manic-depressed manic patients
showed significant elevations in the
urinary output of dopamine on both ad-
mission and discharge from hospital.
A group of schizophrenic patients re-
vealed no over-all difference between the
amounts of adrenalin and noradrenalin
excreted at the time of their admission
to hospital when they were 'sick' and the
values found when they were discharged
as 'recovered'. The magnitude of excre-
tion of these two amines by this group
was at both stages comparable to that of
the group of manic-depressive patients on
discharge. There was no correlation be-
tween catecholamine excretion and clini-
cally rated thought disorder.
The more anxious manic patients were
and the more bodily symptoms they had,
the higher their excretion of noradrenal-
in. In depressed patients the greater the
anxiety and depression, the higher was
18 CANADIAN PSYCHIATRIC ASSOCIATION JOURNAL
the excretion of all three catecholamines
and the fewer were the bodily symptoms.
Acknowledgements
Our thanks are due to Mrs. Margot
Gerstman, Mrs. Evelyn Muth and Mrs.
Elisabeth Rivera who 'performed the bio-
chemical estimations.
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Resume
On a constate que les taux d'adrenaline,
de noradrenaline, de creatinine ainsi que
le volume urinaire etaient reduits d'une
facon significative chez les malades at-
teints de manie depressive, lors de leur
admission a- l'hopital, comparativement a-
ce qu'on a trouve lors de leur depart. On
avance qu'il s'agit peut-etre en partie
d'une alteration metabolique generalisee
qui justifie une plus ample investigation.
Quelques malades atteints de manie de-
pressive ont presente une excretion assez
forte de dopamine tant a- l'admission a-
l'hopital qu'au depart. II est difficile de
savoir ce que signifie cette constatation,
mais une augmentation des amines cere-
brales peut etre accompagnee d'effets
stimulants du systeme central.
Un groupe de schizophrenes n'a pre-
sente aucune difference generale d'excre-
tion de l'adrenaline ou de la noradrenaline
Iorsqu'ils etaient "malades" Iors de leur
admission a- l'hopital et lorsqu'ils s'etaient
"retablis", lors de leur depart ou de leur
separation du groupe des malades atteints
de manie depressive. II n'y avait aucune
correlation entre l'excretion de catechola-
mines et le trouble des idees evalue en
clinique. Ces constatations militent contre
un trouble important du rnetabolisme des
catecholamines dans la schizophrenic.
Plus les malades atteints de manie de-
pressive etaient anxieux, et plus ils se
plaignaient de symptomes corporels, plus
leur excretion de noradrenaline etait
elevee. Chez les malades deprimes, plus
l'anxiete et la depression etaient pro-
fondes, plus l'excretion des trois catechola-
mines etait elevee et moins nombreux
etaienr les symptomes corporels.

They who know the most must mourn the deepest

o'er the fatal truth that the Tree of Knowledge
is not the Tree of Life.

Claudius Buchanan - 1766-1815