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Acta psychiat. scand.

(1981)63,277-289
University Psychiatric Hospital (Head: Prof. Dr. H. Heimann), Tiibingen, West Germany, and Institute of Physics, NLHT, University of Trondheim, Norway

Manic-depressive states and daily temperature


SOME CIRCADIAN STUDIES
B. PPLUG,A. JOHNSSONAND A. TVEITO
EKSE
Proceeding from the hypothesis of disturbed circadian rhythms in
endogenous depression, we observed the oral temperature of four
patients in a long-term study. The results showed the following:
1) Depression is linked to higher mean daily temperatures compared with normal states. In manic states, the mean daily temperature is even higher than in depressive stata. Sleep deprivation
as effective treatment causes a decrease in mean daily temperature.
2) The daily temperature maximum changes its position in depressive states. This is interpreted as indicating a disturbed circadian
system. 3) A period shorter or longer than 24 h c m o t be observed
in depressive states.

Key words: Depression - mania


rhythms - sleep deprivation.

- oral

temperature - circadian

In a previously reported long-term study of a manic-depressive patient (Pflug


et al. (1976)), it was found that the daily temperature pattern was different on
the depressive days compared with normal days. During the depressive periods,
the daily maximum temperature often occurred earlier than during periods
without complaints. The temperature pattern was often different from day to
day and was by no means as stable as during normal periods. Furthermore,
the average daily temperature was higher during the depressive period. Altogether, depressive periods were characterized by disturbed body temperature
functions. As is well known, many functions in man vary according to a daily
pattern. Recordings under constant conditions have also shown that many daily
rhythms are circadian, i.e. pertain to a period of about 24 h (Aschoff & Wever
(1962), Wever (1969)). Kripke et al. (1978) found disturbances in the circadian
system in seven circular manic-depressives. During depression, the circadian
rhythm of the oral temperature was free-running and faster than 24 h. It has
been hypothesized that not only the daily temperature rhythm, but the whole
system of circadian rhythms in man might be disturbed during the depressive
state in manic-depressive patients. In one case, Kripke et al. (1978)found similar
disturbances in the circadian system of urine variables (water and free hydrocortisone) and activity. The hypothesis that disturbed circadian rhythms play an
important role in the pathogenesis of manic-depressive disorders is furthermore
supported by investigations on excretion of electrolytes (Lobban et al. (1963),
0001-690x/81/030277-13 $02.50/0 @ 1981 Munksgaard, Copenhagen

278
Moody & AZZsopp (1969)), neurohumoral metabolites (Riederer et al. (1974)),
biogenic amines in blood plasma (Birkmayer & Linauer (1970), Klempel (1972),
Niskaunen et al. (1976)), magnesium (PfIug (1976)), hormones in blood plasma
(Halberg (1968), Sachur et al. (1973, 1976)) and sleep parameters (Hawkins &
Mendels (1966), Hajnsek et al. (1973), Kupfer (1976)).
In the report by Pflug et at. (1976) mentimed above, the Occurrence of a

period at variance with the normal 24-h rhythm in the oral temperature curves
of one patient was also interpreted as indicating a disorganized circadian system
(desynchronization).
The present report includes new data from the same patient in addition to
measurements on new patients. The report concentrates on the following
problems:
1) Is there a relationship between the daily mean temperature and the depressive state of the patient?
2) Are there differences in the daily temperature pattern of the patients during
depressive and normal periods?
3) Is the frequency content of the temperature data different during depressive
and normal states?
CASE HISTORIES
Care history No. 1
The case history of the manic-depressive patient H.F., born in 1942, has been previously described (Pflug et al. (1976)). U p to January 1975, the patient had had eight
depressive episodes and one manic (1970). From mid-January 1975 until mid-March
1975, she felt well (Fig. 1). After a few slightly euphoric days (March 8-13), she felt
imtable, sometimes aggressive and unbalanced, but there were also days when she
felt well. Until March 1 she was treated with lithium carbonate (plasma level 0.651.12 mEq). During a journey, she stopped taking lithium carbonate until April 25,
but continued the medication afterwards. From April 26 to May 23, she felt well,
then she complained of sleep disturbances, inner restlessness, fatigue, despair and
heart trouble. This state continued until July 2 and could be interrupted by therapeutic
sleep deprivation for 1 or 2 days. From July 3 mward, she was without camplaints
after another sleep deprivation. Except for lithium carbonate, she took no drugs. In

Lithium

I
I

I I

Lithium
I.
Sleep deprivations

1 lllu

I.

M.

I.

Sleep deprivations

1 111-

Fig. 1. History for the investigated period, Patient 1. The following abbreviations are
used: Imipramine = I; Medazepam = M . Black areas denote depression; arrows denote
sleep deprivation; Q = no medication.

279

M
a
p
! Apr

I
May

June

I
July

I
Aug

Sept

Oct

1975

Fig. 2. History for the investigation period, Patient 2. Black areas denote either manic
or depressive state, as indicated.

mid-October, the temperature patterns showed irregularities as during times of depression, although she did not complain. Preventive imipramine treatment led to
nausea and reduced concentration, and was therefore discontinued. The patient felt
well until October 31, after this she felt depressed and tired, complained of a sore
throat, perspiration and anxiety. This state lasted until the beginning of January 1976.
Then she slowly improved. From January 16 onward, she had no complaints. Sleep
deprivation led only to short improvements in this patient, and thymoleptics did not
improve the depression. A second imipramine treatment was stopped on December 27,
and the depression disappeared without thymoleptic drugs.
Case history No. 2
Patient No. 2 was a 56-year-old housewife who had suffered from cyclothymia for
13 years. Her mother had once been treated in hospital for a retarded and stuporous
syndrome and later for disturbance of mood. The patients first episode was manic.
During the one and a half years before examination she had alternating manic and
depressive episodes, lasting from 13 to 35 days, with no symptom-free interval. The
switch from depression to mania occurred abruptly within a few hours, that fram
mania to depression took more than 1 to 2 days. Neither treatment with lithium salts
nor sleep deprivation was successful. After many unsuccessful attempts with different
drugs, only continuous medication with imipramine and clozapine had some effect
on the symptoms. During depression, the dose of imipramine was increased, during
mania the dose of clozapine. During mania, the patient was euphoric, hyperactive,
sexually uninhibited, showed flights of ideas and overestimated herself excessively.
Her relatives could hardly tolerate her during this period. During depression, she was
deeply dejected and her psycho-motoric behaviour was inhibited. She complained of
inner restlessness, a feeling of heaviness in the chest and very disturbed sleep.
Fig. 2 shows the course of the illness, and the medication during the period of
examination.
Case history No. 3
The patient was the 41-year-old wife of a baker and had her first depression when
she was 20. Twice, after delivery, she had had depressive episodes lasting 4 to 6
months. In the years before the investigation, she had depressed episodes either in
spring or autumn. On each of these occasions, she lost about 20 kg in weight, felt
nervous and mentally tense. She lost interest in things and neglected her home. She
suffered from constipation, perspiration, sleep disturbances, and diurnal ups and
downs in mood and drive. During the intervals, she had no complaints, was a wellbalanced, sociable woman, very orderly, reliable and accurate. During the period

280
of her temperature recording, she took neither thymoleptic nor neuroleptic drugs,
though occasionally Lorazepam to get to sleep. When the investigation began during
a depression she weighed 73 kg. In the interval, in April 1977, she weighed 96 kg.
Fig. 3 shows the investigation period.

Case history No. 4


Patient No. 4 was a 56-year-old housewife, working part-time as a seamstress. She
had suffered from cyclothymia since she was 34. During intervals, she was wellbalanced, calm and very reliable. In depressive episodes, she became agitated, despaired, wept often, was not capable of doing her housework and could not go to
work, she lost all interest and suffered from considerable sleep disturbance. During
mania, she was overactive, kept on talking, was euphoric, and in spite of only 2 or
3 hours sleep, she did not get tired. At the beginning of the investigation, she was
suffering from the sixth depressive episode, which had started suddenly early in the
morning. The patient had thoughts of suicide, was agitated, her arms and legs felt
very heavy; she did not get up, and complained about considerable sleep disturbances.
After an interval without complaints, which lasted a week, she was first in a hypomanic and then in a manic state. During the period of investigation, she had a further
depressive episode after an interval without complaints (see Fig. 4).
METHODS
Self-rating and temperature data
The patients were asked to give self-ratings of their mood each day. Only exceptionally did these self-rating estimates deviate from judgements by the doctor
or close relatives. Data presented here are given in a scale from 0 to 2: 0 =
feeling well, 1 = not feeling well, 2 = depressed. Hypomania and mania
states were estimated by the doctor and the relatives.
The recordings of the oral temperature (glass-mercury thermometer) were
taken by the patients every 3 h, except during the night.

Time of occurrence o f temperature maxima


It turned out that the maxima in the temperature rhythms occurred at different
times of the day: they varied between patients, but also in the individual patient. During normal periods, the maxima occurred at the same time, but during
depression, they fluctuated from day to day. As described earlier (Pflug et al.
(1976)) the so-called phase deviation was therefore calculated. The phase deviation simply denotes the deviations - in hours - from the actual time of the

Fob

I March1

Ap

May

June

July

igm

Aug

Sept

Oct

Nw

Dec

Jon

Febr

19n

Fig. 3. History for the investigation period, Patient 3. Black areas denote depressive
periods; @ = no medication.

281
M.
,

F.

I)

P.

M.
F.

Fig. 4. History for the investigation period, Patient 4. The following abbreviations are
used: Maprotilin = M; Lorazepam = L; Perazin = P; Flurazepam = F; @ = no medication. Black areas denote either manic or depressive state, as indicated.

temperature maximum to the time of the day it normally occurred. If a day


had two maxima of the same magnitude, the smallest phase deviation was used
in the calculations.
Analysis of period content in temperature data

The present data were analysed as reported by Ppug et al. (1976) and both
autocorrelation and period analysis techniques were used.
RESULTS
Daily mean temperature and mood of patient
Pflug et al. (1976) found that a depressive state was correlated to a higher tem-

MANIA

HY POMANIA

DEPRESSIVE
STATE 2
DEPRESSIVE
STATE 1

'NORMAL
SELF-RATING

.36.6 36.7

36.8

36.9

37.0

*C

Fig. 5. Temperature and rating o f mood. The dairy average temperature is plotted
versus rating of mood for the four patients in the investigation. Patient 1 = 0; Patient 2 =
Patient 3 =
Patient 4 = x. Typical standard errors of the mean are
indicated for some temperature values.

+;

n;

282
Table 1. Daily average temperature (OC). n = number

!0.03

36.98 $003

- I

11.123

x
self- rating

3671

$001 3675
0

2 values are given as SEM

days

n =56

36.X

of

-7

20023678 $01173691 $00 3699 $003

depress/vo
f

depresswe

bypomanra

I
mama

2AZ

n (n - 1)

perature: days with self-rating 2 were found to have a higher mean temperature,
whereas days with a slight depressive state (1 on the present scale) and normal
days (days with self-rating 0) had a lower mean temperature. New data supporting this conclusion (see Table 1) are plotted in Fig. 5 .
Circles represent data of Patient 1, who had no manic period during the
time these data were collected. The circles represent mean values of all recordings on this patient, from November 1, 1973, to March 22, 1976, and thus
include mean values already presented in Pfrug et al. (1976) (Fig. 4). It is seen
that the daily mean temperature value is about the same when the self-rating
is 0 and 1, but higher when the patient is depressed (self-rating 2).
Plusses give mean values for the depressed and manic state of Patient 2. The
patient was either manic or depressed without normal days (see case history).
The daily mean temperature is evidently highest during the manic period.
Squares show mean values for Patient 3. Here too the depressive periods are
correlated with higher daily mean temperature.
Crosses represent mean values for Patient 4, who showed both depressive
and manic periods. Her state was judged on a scale 0, 1, 2, !hypomania, and
mania. The daily mean temperature shows a gradual increase as depression
becomes deeper or mania evident.
Altogether the new data confirm that depression is associated with a higher
daily mean temperature than the normal state. Manic states seem to be connected with even higher temperatures than depressive ones.
Daily mean temperature and sleep deprivation
Patient 1 was given sleep deprivation for one night at a time on several occasions (see case history). This led to a considerable improvement but, in her
case, only for a short period after each treatment. From the relationship found
in Fig. 5 between daily mean temperature and self-rating, one would predict
that the patients daily temperatures would be lower during the days after the
sleep deprivation, since the treatment lowered the self-rating. Thii was tested
on the data from a total of 16 sleep deprivations.

283

Mood

Temperature

SD

SD

320E

360
i

I
I
I
I

36n
'?OE
1

2E

!I

37.0
361)

!
t

i
360
3ZOE

Fig. 6. Sleep deprivation; its effect on mood and temperature. Left: the influence of
sleep deprivation on mood. Right: the influence on temperature. The small diagrams
include data for successive days before and after sleep deprivation (SD). 6a: Data
from sleep deprivation June 29, 1974; 6b: Data from sleep deprivation July 9, 1974;
6c: Data from sleep deprivation November 7 , 1974; 6d: Average data from 16 sleep
deprivations.

Fig. 6 shows some representative measurements ( 6 a - 6 ~ )and mean values for


all the sleep deprivations available (6d). The figure is divided into two parts,
mood and temperature, showing the patient data some days before and some
days after sleep deprivation (SD). For example, 6a shows that the self-rating
was 2 for 4 days before SD, but changed to 0 for the next 5 days. The SD
was thus very effective. Accompanying this change in the self-rating is also a
lowering of the temperature, see right-hand side of the figure. In the same way,
the sleep deprivations on other occasions (Fig. 6b and 6c) were successful in
bringing the patient - temporarily - from a depressive state to a normal state.
6b specifies that the self-rating was 2 during 2 days immediately before SD
but 0 for the following 3 days, etc. The temperature recordings show that the
tendency to increased mean temperature is broken by the SD.
The mean values for all SD-treatments, Fig. 6d, support the conclusion that
SD was a valuable treatment for this patient and do not weaken the hypothesis
that the daily mean temperature is lowered by the treatment.
Time of daily temperature maximum. Relation to depressive state
The time of the temperature maximum was of interest, since it seemed to vary
with the depressive state (Pflug et al. (1976)). Figs. 7, 8 and 9 present data from

284
TIME

Fig. 7. Time of daily temperature maximum, Pafient 1. The time of the temperature
maximum is plotted for subsequent days (circles). On the left of each row are the
self-ratings for each day. Black areas: self-rating of 2 (depression); hatched areas:
self-rating of I (not feeling well); white areas: self-rating of 0 (feeling dl). Further
details in the text.

Fig. 8. Time of daily temperature maximum, Patient 3. See legend to Fig. 7.

285

Patient 1 (later experimental period), Patient 3 and Patient 4 respectively. Only


parts of the total experimental periods are shown. (Data are not reproduced
for Patient 2, since we do not have data for longer continuous periods; specifically, it was not possible to determine the time for the temperature maximum
when the patient was normal).
Fig. 7 shows that Patient 1 has her temperature maximum at 19.00 h when in
a normal state (see e.g. good period after Aug. 1, 1975). Only the normal periods
are correlated with a stable pattern.
The same observation as reported by Pflug et al. (1976) might be found in
the present data: the patients mood seems to improve, but the patient is not
aware of it or ready to accept it. An example of this is seen at the end of
April 1975 (Fig. 7): the temperature maximum is stable and indicates a normal
state several days before the patient gives stable self-ratings of 0.
Fig. 8 shows that Patient 3 has her daily maximum at 12.00 h during normal
periods, see period after Jan. 1, 1977. Also in her case, normal periods are
correlated with a stable pattern, while depressive periods are characterized by
an unstable back and forth movement of the maximum from day to day.
As seen in Fig. 9, Patient 4 has her temperature maximum at 17.00 h on most
days during her good periods. However, the pattern is less stable than that
during the good periods of Patients 1 and 3. During depression and hypomania,

TIME
8 I4 20
1977

24. Jun

Nor

0c
.

971

.MI

978

MI

Fig. 9. Time of daily temperature maximum, Patient 4. See legend to Fig. 7. Symbols
used in the row to the left fin addition to those explained in Fig. 7): Obliquely hatched
areas: hypomania; Crossed lines: mania.

286
a

= t

..

SELF-RATING

SELF- RATING

Fig. 10. Phase deviation and self-rating during subsequent 2-week intervals. For each
2-week interval, the phase deviation is plotted versus the self-rating of Patient I ( I 0 a)
or Patient 3 ( I 0 b).

the temperature pattern is very unstable, in the manic state, the temperature
maxima often occur at 17.00 h.
To quantify the findings of a more unstable temperature pattern during depressive states, the daily phase deviation was averaged for successive fortnights and plotted versus averaged self-rating for the same periods, see Fig.
10a and lob.
Fig. 10a gives new data for Patient 1 (data not included in Pfiug et al.
(1976)). The correlation coefficient is 0.72, i.e. the same as for earlier measurements on this patient (PfIug et d.(1976)).
Fig. 10b shows the results for Patient 3. The correlation between phase
deviation and self-rating is fairly good, correlation coefficient 0.78.
The few data for the depressive periods of Patient 4 do not allow a reliable
calculation between phase deviation and self-rating (although the correlation
coefficient was of the same magnitude as for Patients 1 and 3). The data are
therefore not reproduced here.

Period analysis
We analysed the period content in the temperature data from Patients 1, 3 and

287
4. The aim was to determine whether the period content was the same during
depression as during intervals (cf. Pflug et al. (1976)).
Autocorrelation analysis was performed on data from normal and bad periods. In general, the analysis confirmed what could be seen from the original
temperature plottings: during normal periods the temperature pattern was
more stable than during depressive periods. The autocorrelation function, there
fore, has a more evident 24-h periodicity during normal states than during depressive ones (cf. representative curves 7b and 7c in Pfiug et al. (1976)); 7b
represents a normal period, 7c a depressive period).
The period content of the temperature data showed the expected 24-h period
but no systematic Occurrence of other periods around 24 h were found. Since
Pfiug et al. (1976) reported an unusually high content of 22.5-h rhythm for a depressive period in Patient 1, special care was taken to analyse for rhythms in
this regimen. We were not able to find in the new data a significant presence
of such a 22.5-h period, either under normal or under depressive conditions.

DISCUSSION

A summary of the findings will perhaps give answers to the questions posed
in the introduction. On the basis of our findings, it is evident that oral daily
temperature is connected to the depressive state. The higher the self-rating, the
more depressive the state, and the higher the temperature. Furthermore, if sleep
deprivations are used to lower the self-rating, the daily mean temperature seems
also to be lowered. From these results, one would predict that whatever successful treatment is used to help a manic-depressive patient, it also lowers the
temperature. Manic phases produced even higher oral temperatures in some
of our patients.
The temperature increase in the depressive or manic episodes might, in general, be the expression of changed conditions in parts of the CNS (e.g. hypothalamus, limbic system). These changed conditions could, in turn, be the
result of counter-acting regulatory mechanisms of disturbed vegetative functions, or could also be direct indicators of stress. The higher mean temperatures
are not a result of thymoleptic or neuroleptic drugs. This is shown by the temperature measurement of Patient 3, who was not treated with these drugs
(Fig. 3).
We would like to mention a finding not directly connected with the temperature measurements. For Patient 3, the weight data show an interesting
development during the time she was under observation: the body weight increased steadily during periods with self-rating 0 or even 1, but stopped increasing, or even diminished, when self-rating was 2, i.e. in the depressive state.
It is, however, difficult to conclude whether this behaviour is due to the mood,
to changed food-intake or to increased metabolism (and temperature!) during
depressive states.
The differences in daily temperature patterns between normal and bad periods
are continned in the present study. We find it striking that the temperature
maximum changes its position so markedly during bad periods, and interpret
19

288
this as an indication of disturbances of the circadian functions of the patients.
However, in the new data, we could not find a significant presence of non-24-h
rhythms in the neighbourhood of 24 h, as found for Patient 1 in her worst
depressive period (Pjlug et al. (1976)). In the worst period, the temperature was
not recorded by the patient herself but by the staff. It might be that the later
oral measurements by the patient every 3rd h acted as a Zeitgeber and influenced the period content of the rhythm, excluding non-24-h periods. This
must be clarified in future work. If such non-24-h rhythms exist in the present
data, they are so weak as to preclude any use of them as a diagnostic tool.
The origin of the changes found in the temperature pattern is not clear. It
could be, for example, that they are the results of disturbances in the coupling
between different oscillators in a circadian system, as discussed by W e v e r
(1975). However, at the present stage, it seems premature to exclude other
explanations.
ACKNOWLEDGEMENT
We would like to thank Prof. Dr. W . Engelmann for his continuous interest in this
work.
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Received June 30, 1980


Burkhard PRug
University Psychiatric Hospital
Osianderstr. 22
D-7400 Tiibmgen
W. Germany
Anders Johnsson
A . Tveito Ekse
Institute of Physics

NJXT
University of Trmdheim
N-7000 Trondheim
Norway

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