Journal of Affective Disorders, 26 (1992) 223-230 0 1992 Elsevier Science Publishers B.V. AH rights reserved 01650327/92/$05.00
223
JAD 00948
rain
horous metabolis orus- 1 mag
nance spectrosco
Tadafumi Kato a, Saburo Takahashi a, Toshiki Shioiri a and Toshiro Inubushi b n Department of Psychiatry, h Molrcularneurobiology Research Center, Shiga University of Medical Science, Shiga, Japan (Received 30 April 1992) (Revision received 30 July 1992) (Accepted 7 August 1992)
Summary Brain phosphorus metabolism was measured in 22 patients with depressive disorders. Ten of them had DSM-IlI-R bipolar disorder, and 12 had major depression. In bipolar patients, phosphomonoester (PME) and intracellular pH were significantly increased in the depressive state than in the euthymic state, while those values in the euthymic state were significantly low as compared to age-matched normal controls. Phosphocreatine (PCr) was significantly decreased in severely depressed patients compared to mild depressives. These findings suggest that high energy phosphate metabolism, intracellular pH and membrane phospholipid metabolism are altered in depressive disorders.
Key words: Bipolar disorder; Depression; Magnetic Phosphocreatine; Phosphomonoester
Introduction Depressive symptoms are common in patients with any kinds of brain dysfunction such as brain injury, cerebrovascular diseases, endocrinologic diseases and neurodegenerative disorders. Bipolar depression and unipolar depression are two major types of depressive disorders, and re-
Correspondence to: T. Kato, Department of Psychiatry, Shiga University of Medical Science, Seta-tsukinowa-cho, Otsu, Shiga, 520-21, Japan
resonance
spectroscopy;
Intracellular
pH;
searchers in psychiatry have focused on the pathophysiology of these disorders to find many facts which suggest certain brain dysfunction existing in these disorders: lowered glucose metabolism detected by positron emission tomography (Buchsbaum et al., 1986; Kishimoto et al., 1987; Baxter et al., 1989; Martinot et al., 19901, lowered cerebral blood flow (Mathew et al., 1980; Uytdenhoef et al., 1983), changes in (Y wave activity in electroencephalography and abnormal pattern of evoked potentials (Shagass, 1983). Whether or not abnormal brain energy metabolism underlies in depressive disorders hx not been investigated so far.
Phosphorus-31 magnetic resonance spectroscopy (31P-MRS) can detect high energy phosphate metabolism and membrane phospholipid metabolism in vivo in humans, which can be used in clinical settings. Abnormal brain phosphorous metabolism has been reported in Alzheimer’s disease (Brown et al., 1986), schizophrenia (Pettegrew et al., 1991; O’Callgahan et al., 1991; Williamson et al., 1991), mania (Kate et al., 1991) and AIDS dementia (Bottomley et al., 1991). To
our knowledge there is no report on “P-MRS in depressive disorders so far. Much evidence implicates prefrontal cortex dysfunction in mood rlisorders, e.g. abnormal glucose metabolism (Buchsbaum et al., 1985; Baxter et dl., 1989; Martinot et al., 1990) and decreased uptake of L-[“CIS-hydroxytryptophan (Agren et al., 1991). We examined the area including frontal cortex in depressive patients not only for the above mentioned reason, but nuclear magnetic resonance (NMR)
TABLE 1 Patient characteri: tics age
WX
HRSD
28
33 3Y
F F F
31 16 30
4 Bipolar, mild
44
F
2x
5 Bipolar, moderate
44
F
21
6 Bipolar, moderate 7 Bipolar, moderate
56 31
F M
I8 24
46 49 so
M hl M
21 18 29
‘0 24 32
F F F
14 Rec. Severe
34
15 Ret, Severe. with melancholia 16 Rec. with psychotic Features, Mood Congruent I7 Single, severe. with melancholia 18 Ret, Moderate 19 Single, Mild 20 Ret, Moderate, seasonal 21 Ret, Severe 22 Single, Mild
Bipolar disorder Case diagnosis 1 Bipolar Disorder. not otherwke specified 2 Bipolar, mild 3 Bipolar, moderate
8 Bipolar. with psychotic features. mood congruent Y Bipolar. moderate 10 Bipolar, mild Major depression 11 Single, Moderate 12 Ret, Mild, Seasonal 13 Ret, Moderate
Medication depressed
Li 800 mg MIA 60 mg, HP 4.5 mg. BPD 3 mg CXZ 6 mg, LP 25 mg, PMZ 25 mg Li 800 mg, APZ 1.2 mg. THY 100 ug Li l(1111) mg. TMP 75 mg
Euthymic
Li 600 mg Li X00 mg
Li 600 mg. LP SOmg
_
Li 600 mg. THY 100 ug Li 1000 mg, LP 75 mg, THP 6 mg CMP 225 mg Li 600 mg, AMP 150 mg. DZP 6 mg
-
Li 600 mg Li 1200 mg Li 600 mg, CMP 100 mg
15 20 15
CMP 75 mg
MIA 60 mg, IMP 75 mg
F
25
CMP 75 mg, BZP 5 mg
40
F
13
CMP 75 mg
Li 600 mg, CMP 150 mg, AMI 150 mg CMP 100 mg, LP 25 mg, APZ 1.2 mg CMP 100 mg
50 59 22 23 30 3Y 50
F F M M M M M
20 34 24 1.5 14 32 17
CMP 75 mg, CXZ 6 mg CMP 150 mg, BZP 5 mg IMP 75 mg CMP 225 mg, DZP 6 mg CMP 225 mg
CMP 150 mg, BZF 5 mg IMP 150 mg CMP 75 mg CMP 150 mg, DZP 6 mg CMP 225 mg CMP 150 mg, ETZ 1 mg
AMP-amitriptyline; CMP-clomipramine; IMP-imipramine; MIA-mianserin; TMP-trimipramine; APZ-alprazolam; BZP-bromazepam; CXZ-cloxasolam; DZP-diazepam; ETZ-etizolam; HP-haloperidol; LP-levomepromazine; BPD-biperiden; THP-trihexyphenidil; PMZ-promethazine; HRSD = Hamilton Rating Scale for Depression.
225
spectra can be easily recorded from this area using surface coils, in an attempt to make bipoiar-unipolar comparison.
ATP Depressive PME
11.7
Subjects
PCr 10.0
Subjects examined in this study were 22 depressive patients. They were diagnosed to have DSM-III-R major depression (N = 12, age + SD = 35.3 + 12.1) or bipolar disorder depression (N = 10, age + SD = 42.0 + 8.6). They were evaluated in two interview sessions, for an hour respectively, by two senior psychiatrists. They recorded whether or not the patients met each item of diagnostic criteria of major affective disorders in DSM-III-R (American Psychiatric Association, 1987). Only patients whose interview results led to the same diagnosis after two seperate interviews were included in this study. All patients were hospitalized in Shiga University of Medical Science Hospital. They were all under treatment with antidepressants, lithium carbonate, hypnotics and antipsychotics prescribed by the attendant clinicians. Normal controls whose ages (within 3 years) and sexes matched the patients were also investigated. The controls were healthy hospital workers without any past history of psychiatric disorders. All subjects gave v+!;ul. ttcn informed consent. Patients aged above 60 were excluded from this study. The Hamilton Rating Scale for Depression (HRSD) was scored on the day of MRS examination. Profiles of the patients are listed in Table 1.
pH
Method The method of MRS data acquisition is basically the same as described in our previous report (Kate et al., 1991). Subjects were examined on a l.ST GE SIGNA MR system equipped w-ith a spectroscopy package. Subjects lay down with their orbitomeatal line (OM line) vertical to the axis of the magnet. Surface coils for 1H and “P supplied as option from the manufacturer, General Electric (GE), were used. Diameter of the coils were 20 cm for the transmitter and 7.5 cm for the receiver. The surface coil for proton was placed over their heads using a custom-built stand, an edge of the coil being set above the tip of
'-O*
Euthymic PME 6.0 PCr 13.8 pH
6.99
Control PME ;.; Per 14.1 pH
I
I
I
I
I
Fig. 1. “P “P
NMR
NMR
-20
spectra in a patient
spectra of frontal
PPM
and a normal
control.
lobe in a bipolar patient (case 5.
44 years old) and an age-matched tion frequency
I
,
n
7.03
was 25.85 MHz,
normal control.
repetition
Observa-
time 3 s, 128 aver-
ages. The top spectrum shows that obtained
in the depressive
state, and middle in the euthymic state. The bottom spectrum shows that of a control. phocreatine
(PCr)
tracellular
Phosphomonoester
(PME)
peaks show state-dependent
and phos-
alteration.
In-
pH is low in the middle spectrum.
nose ‘H MRI was obtained and a volume of interest (VOID was determined as the center 30 mm slice between the front pole and the front edge of corpus callosum. The magnetic field over the VOI was optimized by water signals enough to establish the line width less than 10 Hz. Without moving the position, the ‘H coil was replaced with the ‘iP coil, then “P NMR spectra were obtained using depth-resolved surface coil spectroscopy (DRESS) pulse sequence (Bottomley et al., 1984). This can determine the VOl with a magnetic field gradient and a surface coil to have the VOI shaped disk-like and parallel with a surface coil. The position of the VOI was SO carefully determined that the region examined was practically identical for each trial. Repetition
22h
Inter-assay intra-individual coefficients of variation (CVs) were examined by “P MRS data acquisition from a euthymic bipolar p ‘ient for eight examinations repeated every week, and a manic patient for six examinations. CVs of the data were 8.3% and 5.0% for PME/total (total phosphorus compounds), 7.9% and 9.8% for PCr/total and 0.66% and 0.29% for pH, respectively, which were smaller than inter-individual CVs in normal subjects, 14.7% for PME, 10.6% for PCr and 0.72% for PH. For statistical analysis, two-tailed paired t-test, two-sample t-test and test for equal variance (Ftest) were used.
time (TR) was set at 3 s. One hundred twentyeight scans were averaged. Total time for examination was about 25 min. FIDs were processed using GE 1280 DATA station with GEN software. (see Fig. 1). Broad peaks and baseline distortion were cancelled using convolution difference method (Campbell et al., 1973); a spectrum with 15 Hz line broadening was subtracted by a spectrum with 150 Hz line broadening multiplied by the constant, k = 0.85. Baseline correction was applied to the phase-corrected spectra. Peak areas were calculated by manual curve fitting according to the Pettegrew’s method (Pettegrew et al., 1991). Details of the method were described elsewhere (Rat0 et al., 1991). Seven peaks assigned as phosphomonoester (PME), inorganic phosphate (Pi), phosphodiester (PDE), creatine phosphate (PCr) and three phosphorus signals from nucleotide triphosphate, mainly adenosine triphosphate (ATP), were examined (see Fig. 1). Data of these metabolites were shown as peak area ratio to the total peak area. Intracellular pH was calculated from the difference of chemical shifts between Pi and PCr (Petroff et al., 1985)
esults Table 2 shows the 3’P NMR data. Significant differences were found in PME and pH. In bipolar patients, PME and pH were higher in the depressive state (PME: 11.8 + 2.1, P < 0.05, pH: 7.06 f 0.05, P < 0.05) thau in the euthymic state (PME: 9.4 _t 1.7, pH: 7.00 + 0.04). These values in the euthymic state (PME: P < 0.002, pH: P < 0.002) were lower than the values in normal controls (PME: 12.2 + 1.4, pH: 7.07 f 0.041 and com-
TABLE 2 Phosphorus metabolites profile in depressive patients
Bipolar Depressed n = 10
’ dn SD
age
HRSD
PME
Pi
PDE
PCr
y-ATP
(Y-ATP
P-ATP
pH
42.0 8.6
24.2 5.3
11.8 2.1 1
5.7 2.1
20.4 4.2
12.3 1.8
10.3 1.2
25.8 2.8
13.7 1.R
7.06 0.05 1
9.4 j 1.7 1 *** 12.2 J 1 1.4
6.0 2.2
20.2 3.4
13.8 1.6
10.5 1.5
25.7 3.3
14.3 3.6
5.3 1.2
19.7 1.9
13.5 1.1
10.1 1.4
25.0 1.6
14.3
7.00 ; 0.04 1 *** 7.07 J 1 0.04 **
11.2 2.1
5.8 2.1
19.2 4.6
13.1 1.9
10.5 1.7
26.7 3.8
13.5 2.3
7.06 0.08
Bipolar Euthymic n = 10
41.9 8.4
Control n= 10
40.8 9.1
Major Depression n = 12
35.3 12.1
Major Dep, Euthymic n = 12
35.3 12.1
12.6 3.0
5.3
19.5
13.3
10.0
24.6
14.6
1.1
2.6
1.7
1.3
3.2
3.0
7.10 0.08
Control n = 12
36.1 11.5
li.6 1.6
S.! 1.1
20.3 2.1
13.0 1.5
10.3 1.3
25.5 2.2
14.2 1.4
7.06 0.04
20.3 6.8
*
1.1
*p
223
JAD 00948
rain
horous metabolis orus- 1 mag
nance spectrosco
Tadafumi Kato a, Saburo Takahashi a, Toshiki Shioiri a and Toshiro Inubushi b n Department of Psychiatry, h Molrcularneurobiology Research Center, Shiga University of Medical Science, Shiga, Japan (Received 30 April 1992) (Revision received 30 July 1992) (Accepted 7 August 1992)
Summary Brain phosphorus metabolism was measured in 22 patients with depressive disorders. Ten of them had DSM-IlI-R bipolar disorder, and 12 had major depression. In bipolar patients, phosphomonoester (PME) and intracellular pH were significantly increased in the depressive state than in the euthymic state, while those values in the euthymic state were significantly low as compared to age-matched normal controls. Phosphocreatine (PCr) was significantly decreased in severely depressed patients compared to mild depressives. These findings suggest that high energy phosphate metabolism, intracellular pH and membrane phospholipid metabolism are altered in depressive disorders.
Key words: Bipolar disorder; Depression; Magnetic Phosphocreatine; Phosphomonoester
Introduction Depressive symptoms are common in patients with any kinds of brain dysfunction such as brain injury, cerebrovascular diseases, endocrinologic diseases and neurodegenerative disorders. Bipolar depression and unipolar depression are two major types of depressive disorders, and re-
Correspondence to: T. Kato, Department of Psychiatry, Shiga University of Medical Science, Seta-tsukinowa-cho, Otsu, Shiga, 520-21, Japan
resonance
spectroscopy;
Intracellular
pH;
searchers in psychiatry have focused on the pathophysiology of these disorders to find many facts which suggest certain brain dysfunction existing in these disorders: lowered glucose metabolism detected by positron emission tomography (Buchsbaum et al., 1986; Kishimoto et al., 1987; Baxter et al., 1989; Martinot et al., 19901, lowered cerebral blood flow (Mathew et al., 1980; Uytdenhoef et al., 1983), changes in (Y wave activity in electroencephalography and abnormal pattern of evoked potentials (Shagass, 1983). Whether or not abnormal brain energy metabolism underlies in depressive disorders hx not been investigated so far.
Phosphorus-31 magnetic resonance spectroscopy (31P-MRS) can detect high energy phosphate metabolism and membrane phospholipid metabolism in vivo in humans, which can be used in clinical settings. Abnormal brain phosphorous metabolism has been reported in Alzheimer’s disease (Brown et al., 1986), schizophrenia (Pettegrew et al., 1991; O’Callgahan et al., 1991; Williamson et al., 1991), mania (Kate et al., 1991) and AIDS dementia (Bottomley et al., 1991). To
our knowledge there is no report on “P-MRS in depressive disorders so far. Much evidence implicates prefrontal cortex dysfunction in mood rlisorders, e.g. abnormal glucose metabolism (Buchsbaum et al., 1985; Baxter et dl., 1989; Martinot et al., 1990) and decreased uptake of L-[“CIS-hydroxytryptophan (Agren et al., 1991). We examined the area including frontal cortex in depressive patients not only for the above mentioned reason, but nuclear magnetic resonance (NMR)
TABLE 1 Patient characteri: tics age
WX
HRSD
28
33 3Y
F F F
31 16 30
4 Bipolar, mild
44
F
2x
5 Bipolar, moderate
44
F
21
6 Bipolar, moderate 7 Bipolar, moderate
56 31
F M
I8 24
46 49 so
M hl M
21 18 29
‘0 24 32
F F F
14 Rec. Severe
34
15 Ret, Severe. with melancholia 16 Rec. with psychotic Features, Mood Congruent I7 Single, severe. with melancholia 18 Ret, Moderate 19 Single, Mild 20 Ret, Moderate, seasonal 21 Ret, Severe 22 Single, Mild
Bipolar disorder Case diagnosis 1 Bipolar Disorder. not otherwke specified 2 Bipolar, mild 3 Bipolar, moderate
8 Bipolar. with psychotic features. mood congruent Y Bipolar. moderate 10 Bipolar, mild Major depression 11 Single, Moderate 12 Ret, Mild, Seasonal 13 Ret, Moderate
Medication depressed
Li 800 mg MIA 60 mg, HP 4.5 mg. BPD 3 mg CXZ 6 mg, LP 25 mg, PMZ 25 mg Li 800 mg, APZ 1.2 mg. THY 100 ug Li l(1111) mg. TMP 75 mg
Euthymic
Li 600 mg Li X00 mg
Li 600 mg. LP SOmg
_
Li 600 mg. THY 100 ug Li 1000 mg, LP 75 mg, THP 6 mg CMP 225 mg Li 600 mg, AMP 150 mg. DZP 6 mg
-
Li 600 mg Li 1200 mg Li 600 mg, CMP 100 mg
15 20 15
CMP 75 mg
MIA 60 mg, IMP 75 mg
F
25
CMP 75 mg, BZP 5 mg
40
F
13
CMP 75 mg
Li 600 mg, CMP 150 mg, AMI 150 mg CMP 100 mg, LP 25 mg, APZ 1.2 mg CMP 100 mg
50 59 22 23 30 3Y 50
F F M M M M M
20 34 24 1.5 14 32 17
CMP 75 mg, CXZ 6 mg CMP 150 mg, BZP 5 mg IMP 75 mg CMP 225 mg, DZP 6 mg CMP 225 mg
CMP 150 mg, BZF 5 mg IMP 150 mg CMP 75 mg CMP 150 mg, DZP 6 mg CMP 225 mg CMP 150 mg, ETZ 1 mg
AMP-amitriptyline; CMP-clomipramine; IMP-imipramine; MIA-mianserin; TMP-trimipramine; APZ-alprazolam; BZP-bromazepam; CXZ-cloxasolam; DZP-diazepam; ETZ-etizolam; HP-haloperidol; LP-levomepromazine; BPD-biperiden; THP-trihexyphenidil; PMZ-promethazine; HRSD = Hamilton Rating Scale for Depression.
225
spectra can be easily recorded from this area using surface coils, in an attempt to make bipoiar-unipolar comparison.
ATP Depressive PME
11.7
Subjects
PCr 10.0
Subjects examined in this study were 22 depressive patients. They were diagnosed to have DSM-III-R major depression (N = 12, age + SD = 35.3 + 12.1) or bipolar disorder depression (N = 10, age + SD = 42.0 + 8.6). They were evaluated in two interview sessions, for an hour respectively, by two senior psychiatrists. They recorded whether or not the patients met each item of diagnostic criteria of major affective disorders in DSM-III-R (American Psychiatric Association, 1987). Only patients whose interview results led to the same diagnosis after two seperate interviews were included in this study. All patients were hospitalized in Shiga University of Medical Science Hospital. They were all under treatment with antidepressants, lithium carbonate, hypnotics and antipsychotics prescribed by the attendant clinicians. Normal controls whose ages (within 3 years) and sexes matched the patients were also investigated. The controls were healthy hospital workers without any past history of psychiatric disorders. All subjects gave v+!;ul. ttcn informed consent. Patients aged above 60 were excluded from this study. The Hamilton Rating Scale for Depression (HRSD) was scored on the day of MRS examination. Profiles of the patients are listed in Table 1.
pH
Method The method of MRS data acquisition is basically the same as described in our previous report (Kate et al., 1991). Subjects were examined on a l.ST GE SIGNA MR system equipped w-ith a spectroscopy package. Subjects lay down with their orbitomeatal line (OM line) vertical to the axis of the magnet. Surface coils for 1H and “P supplied as option from the manufacturer, General Electric (GE), were used. Diameter of the coils were 20 cm for the transmitter and 7.5 cm for the receiver. The surface coil for proton was placed over their heads using a custom-built stand, an edge of the coil being set above the tip of
'-O*
Euthymic PME 6.0 PCr 13.8 pH
6.99
Control PME ;.; Per 14.1 pH
I
I
I
I
I
Fig. 1. “P “P
NMR
NMR
-20
spectra in a patient
spectra of frontal
PPM
and a normal
control.
lobe in a bipolar patient (case 5.
44 years old) and an age-matched tion frequency
I
,
n
7.03
was 25.85 MHz,
normal control.
repetition
Observa-
time 3 s, 128 aver-
ages. The top spectrum shows that obtained
in the depressive
state, and middle in the euthymic state. The bottom spectrum shows that of a control. phocreatine
(PCr)
tracellular
Phosphomonoester
(PME)
peaks show state-dependent
and phos-
alteration.
In-
pH is low in the middle spectrum.
nose ‘H MRI was obtained and a volume of interest (VOID was determined as the center 30 mm slice between the front pole and the front edge of corpus callosum. The magnetic field over the VOI was optimized by water signals enough to establish the line width less than 10 Hz. Without moving the position, the ‘H coil was replaced with the ‘iP coil, then “P NMR spectra were obtained using depth-resolved surface coil spectroscopy (DRESS) pulse sequence (Bottomley et al., 1984). This can determine the VOl with a magnetic field gradient and a surface coil to have the VOI shaped disk-like and parallel with a surface coil. The position of the VOI was SO carefully determined that the region examined was practically identical for each trial. Repetition
22h
Inter-assay intra-individual coefficients of variation (CVs) were examined by “P MRS data acquisition from a euthymic bipolar p ‘ient for eight examinations repeated every week, and a manic patient for six examinations. CVs of the data were 8.3% and 5.0% for PME/total (total phosphorus compounds), 7.9% and 9.8% for PCr/total and 0.66% and 0.29% for pH, respectively, which were smaller than inter-individual CVs in normal subjects, 14.7% for PME, 10.6% for PCr and 0.72% for PH. For statistical analysis, two-tailed paired t-test, two-sample t-test and test for equal variance (Ftest) were used.
time (TR) was set at 3 s. One hundred twentyeight scans were averaged. Total time for examination was about 25 min. FIDs were processed using GE 1280 DATA station with GEN software. (see Fig. 1). Broad peaks and baseline distortion were cancelled using convolution difference method (Campbell et al., 1973); a spectrum with 15 Hz line broadening was subtracted by a spectrum with 150 Hz line broadening multiplied by the constant, k = 0.85. Baseline correction was applied to the phase-corrected spectra. Peak areas were calculated by manual curve fitting according to the Pettegrew’s method (Pettegrew et al., 1991). Details of the method were described elsewhere (Rat0 et al., 1991). Seven peaks assigned as phosphomonoester (PME), inorganic phosphate (Pi), phosphodiester (PDE), creatine phosphate (PCr) and three phosphorus signals from nucleotide triphosphate, mainly adenosine triphosphate (ATP), were examined (see Fig. 1). Data of these metabolites were shown as peak area ratio to the total peak area. Intracellular pH was calculated from the difference of chemical shifts between Pi and PCr (Petroff et al., 1985)
esults Table 2 shows the 3’P NMR data. Significant differences were found in PME and pH. In bipolar patients, PME and pH were higher in the depressive state (PME: 11.8 + 2.1, P < 0.05, pH: 7.06 f 0.05, P < 0.05) thau in the euthymic state (PME: 9.4 _t 1.7, pH: 7.00 + 0.04). These values in the euthymic state (PME: P < 0.002, pH: P < 0.002) were lower than the values in normal controls (PME: 12.2 + 1.4, pH: 7.07 f 0.041 and com-
TABLE 2 Phosphorus metabolites profile in depressive patients
Bipolar Depressed n = 10
’ dn SD
age
HRSD
PME
Pi
PDE
PCr
y-ATP
(Y-ATP
P-ATP
pH
42.0 8.6
24.2 5.3
11.8 2.1 1
5.7 2.1
20.4 4.2
12.3 1.8
10.3 1.2
25.8 2.8
13.7 1.R
7.06 0.05 1
9.4 j 1.7 1 *** 12.2 J 1 1.4
6.0 2.2
20.2 3.4
13.8 1.6
10.5 1.5
25.7 3.3
14.3 3.6
5.3 1.2
19.7 1.9
13.5 1.1
10.1 1.4
25.0 1.6
14.3
7.00 ; 0.04 1 *** 7.07 J 1 0.04 **
11.2 2.1
5.8 2.1
19.2 4.6
13.1 1.9
10.5 1.7
26.7 3.8
13.5 2.3
7.06 0.08
Bipolar Euthymic n = 10
41.9 8.4
Control n= 10
40.8 9.1
Major Depression n = 12
35.3 12.1
Major Dep, Euthymic n = 12
35.3 12.1
12.6 3.0
5.3
19.5
13.3
10.0
24.6
14.6
1.1
2.6
1.7
1.3
3.2
3.0
7.10 0.08
Control n = 12
36.1 11.5
li.6 1.6
S.! 1.1
20.3 2.1
13.0 1.5
10.3 1.3
25.5 2.2
14.2 1.4
7.06 0.04
20.3 6.8
*
1.1
*p
