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Effects of sleep deprivation: The phosphorus

metabolism in the human brain measured by P-
31-magnetic resonance spectroscopy

Article in Psychiatry and Clinical Neurosciences May 1999

DOI: 10.1046/j.1440-1819.1999.00487.x Source: PubMed

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Psychiatry and Clinical Neurosciences (1999), 53, 199201

Biological Rhythm
Effects of sleep deprivation: The phosphorus
metabolism in the human brain measured by
31
P-magnetic resonance spectroscopy
JUN MURASHITA, md,1,2 NAOTO YAMADA, md,1 TADAFUMI KATO, md,2
MASAYOSHI TAZAKI md,3 AND NOBUMASA KATO, md1,2
1
Department of Psychiatry, Shiga University of Medical Science, 2Department of Neuropsychiatry, Faculty of
Medicine, University of Tokyo, 3Shiga Mental Health Center Hospital, Shiga, Japan

Abstract Sleep deprivation (SD) has an antidepressant effect in some, but not all, patients with
depression, although its biological mechanisms have not yet been characterized. We previously
reported altered brain phosphorus metabolism measured by phosphorus-31 magnetic resonance
spectroscopy (31P-MRS) in patients with bipolar depression. We preliminarily examined effects
of SD on phosphorus metabolism in the frontal lobes of 15 normal subjects using 31P-MRS.
No significant differences of membrane phospholipid metabolism, high-energy phosphate
metabolism and intracellular pH were found between before and after SD in these subjects.
Further studies will be necessary to elucidate the physiological mechanism of SD for depressive
patients.

Key words depression, frontal lobes, magnetic resonance spectroscopy, sleep deprivation.

INTRODUCTION intracellular pH was increased in the depressive state

compared with those in the euthymic state in the
Sleep deprivation (SD) has been reported to be
frontal lobes of patients with bipolar disorder.5
effective for depression,1,2 especially for bipolar
Therefore, we postulated that SD, which ameliorates
depression, and in some cases some patients have
bipolar depression, may affect these parameters
been reported to be switched into a manic state. Only
measured by 31P-MRS. In this study, we examined
two studies reported functional alteration of human
brain phosphorus metabolism using 31P-MRS in 15
brain after SD. Ebert et al.3 examined patients
normal subjects before and after SD to elucidate the
with major depression responded to SD using single
biochemical mechanisms of SD.
photon emission computed tomography (SPECT)
and found that cerebral blood flow in the anterior
cingulate was decreased after SD. Wu et al.4 also SUBJECTS AND METHODS
suggested that SD was effective only in patients with
The subjects were 15 normal males (1827 years old)
depression who showed high glucose metabolism
recruited from students of the Shiga University of
in the cingulate gyrus using positron emission
Medical Sciences. The first 31P-MR spectrum was
tomography (PET).
obtained in the morning of the first day. In the first
To our knowledge, there is no report of effects
day, they were instructed not to sleep at all that night.
of SD on phosphorus metabolism measured by
31
It was confirmed by an attendant staff member that
P-magnetic resonance spectroscopy (31P-MRS). We
they did not sleep that night. In the morning of
previously reported that phosphocreatine (PCr) was
the second day, the second 31P-MR spectrum was
decreased and the phosphomonoester (PME) and
obtained.
They gave written informed consent to participate
in the present study.
MRS data were acquired with a SIGNA 1.5 Tesla
Correspondence address: Jun Murashita, Department of Psychiatry, MR system (GE Medical System, Milwaukee, USA)
Shiga University of Medical Science, Otsu, Shiga 520-2121, Japan. with a standard spectroscopy package and surface
200
Figure 1. Alteration of phosphorus metabolism in the
frontal lobe before and after sleep deprivation. There were
no significant differences of phosphomonoester (before:
13.5 9.3; after: 14.7 10.0), phosphocreatine (before: 13.3
2.6: after: 12.8 8.8) and intracellular pH (before: 7.08 0.01;
after: 7.09 0.00), between these values before SD and
those after SD.
J. Murashita et al.
coils for 1H and 31P supplied by the manufacturer.
Subjects lay down in such a position that their
orbitomeatal line (OM line) was vertical to the
stretcher. A surface coil for 1H-MRS was placed over
their heads using a hand-built stand. The magnetic
field over the volume of interest (VOI) was optimized
by water signals enough to establish the line width of
less than 10 Hz. Without moving the subjects head
position, the 1H coil was replaced with a 31P coil, then
31
P-MR spectra were obtained from the frontal lobes
using depth-resolved surface coil spectroscopy
(DRESS) pulse sequence. The position of the VOI
was so carefully determined that the region examined
was practically identical for each trial.
Seven peaks assigned as PME, inorganic phosphate
(Pi), phosphodiester (PDE), creatine phosphate
(PCr) and three phosphorus signals from adenosine
triphosphate, were examined. These peak values
were shown as percent values of the total phos-
phorus signal (peak area %). Intracellular pH was
calculated from the chemical shift difference of PCr
and Pi.
Paired t-test was applied for the statistical analysis.
RESULT
Data from one subject were excluded because of
insufficient signal-to-noise ratio. In the other 14
subjects, the peak areas and intracellular pH before
and after SD were compared by paired t-test. There
were no significant differences of these peak area
percentages and intracellular pH, between these
values before SD and those after SD. We could not
find statistically significant differences in all the values
before SD between two groups in which the values
increased or decreased except intracellular pH
before SD (increased, 7.04 0.01; decreased, 7.14
0.00, respectively) (P < 0.05).
DISCUSSION
In this study, there were no significant differences of
31
P-MR variables before and after SD. In other words,
the changes of all metabolites were divided into two
patterns; increased in some subjects and decreased in
others.
Ebert et al. reported that five of ten patients were
identified as responders and others as non-responders
after SD.1 Wu et al. also reported that, of the 15
depressed patients, only four were identified as
responders.4 Therefore, there might also be an inter-
individual difference of metabolic response to SD
in normal subjects. Or there may be a regional
difference of metabolic response to SD in the frontal
Effects of sleep deprivation
lobe, which might have obscured the results, because
effects of SD on the cerebral blood flow was found
only in the anterior cingulate.3 Further studies using
31
P-MR spectroscopic imaging in a larger population
of normal subjects and depressive patients would be
helpful to clarify the metabolic response to SD.
To our knowledge, this is the first study measuring
the phosphorus metabolism in the human brain
before and after sleep deprivation.
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