878
BIOL PSYCHIATRY 1991;29:878-886
Depression, Natural Killer Cell Activity, and Cortisol Secretion Andrew H. Miller, Gregory M. Asnis, C Uriel Halbreich, and Allen J. Norin
stine Lackner,
Natural killer (NK) cell activity was evaluated in 34 ambulatory patients with Major Depressive Disorder (MDD) and 21 healthy controls. No mean differences between the groups were found. However, female depressives (n = 19) exhibited higher NK activity than female controls (n = 14). The relationship between cortisol secretion and NK activity was examined using an integrated cortisol value derived from multiple blood samples taken between 1.00 and 4.00 P~¢. This comprehensive assessment of cortisol secretion circumvents spurious ',single stick" cortisol values and provides a more accurate determination of hypercortisolemia than the dexamethasone suppression test. NK activity in depressives with cortisol hypersecretion (>11 Itgldl) (n = 7) was no different than NK activity ~ depressives and controls with normal cortisol secretion. Furthermore, there was no correlation between cortisol secretion and NK activity in any of the groups. These results indicate that decreased NK activity is not a consistent finding in MDD and cannot be predicted by the presence of hypercortisolemia in these patients.
Introduction Although five studies have reported decreased natural killer (NK) cell activity in patients with Major Depression (MD) (Irwin et al 1987, 1990a; Urch et al 1988; Nerozzi et al 1989; Kronfol et ai 1989), lowered NK cell function in MD has not been a consistent finding (Mohl et al 1987; Schleifer et al 1989). In a large study examining 91 patients d i a ~ n n ~ d w i t h ] ~ i n r Dept~,,ssive r~i~n,a,~. (MDD) and o t o.,,. and . . . . . o,.t,~a ,,,,.,.,,,,~o ne mean differences in NK cell activity were found between groups (Schleifer et al 1989). Furthermore. in this study, no mean differences were noted between depressives and controls in the lymphocyte proliferative response to three mitogens. Nevertheless. advancing age and increasing severity of depression were associated with lowered mitogeninduced proliferative responses in the depressed group. No such relationships were seen for NK cell activity. The authors concluded that altered immune function did not appear to be a specific biological correlate of depression but may occur in subgroups of depressed 'O'
~va
LI&¢I'W,~&
~¢ I
<~
=
OlkcA~llggllk~ll~dl
~lkBlllJIJclt.~
From the Mount Sinai School of Medicine (AHM, CL), New York, HY; the Albert Einstein College of Medicine (GMA), New York, NY; the State University of New York (UH), Buffalo, New York; and the State University of New York (AIN), Brooklyn, NY. Address reprint reo, w.sts to Andrew H. Miller, M.D., Box 1229 Annenberg 22-66, Mount Sinai School of Medicine, l Gustave L. Levy Place, New York, NY I0029. Received May 12, 1990, revised November 16, 1990.
© 1991 Society of Biological Psychiatry
0006-3223/91/$03.50
Depression, NK Activity, Cortisol ~cretion
em~. PSVCH~TaV
8"/9
199l ; 2 9 : 8 7 1 ~ ; 6
patients. Which subgroups of depressed individuals may exhibit alterations in NK activity remains unclear. One possibility may be those depressives who exhibit hypercortisolemia. Twenty percent to 55% of patients with MD exhibit c o . s o l hy-persecretion depending on a variety of factors including age. hospitalization status, and severity of depression (Asnis et al 1981a, 1982, 1989; Haibreich et al 1984; Asnis and l~mus 1987). In addition, NK cell function has been shown to be inhibited by corticosterot~ both in vitro ~ in vivo (Herberman 1982; Djeu et al 1979; Parillo and Fauci 1978; Miller et al 1987). and animal studies have indicated that corticosteroids are capable of mediating stress-induced alterations in cellular immune function of peripheral blood mononuclear cells (Rabin et al 1990). A number of studies have evaluated cortisol secretion and cellular immune function in the peripheral blood of depressed individuals versus control subjects (Syvalahti et. al !985: gronfol and House 1985; Exonfol et al 1985, 1986; Darko et al 1988a, 1988b; Nerozzi et al 1989; Schleifer et al 1989), and the results have t ~ e d to confirm a relationship between these two variables. Nevertheless, the majority of these studies have used either "single stick" measures of plasma cortiso! or the dexamethasone suppression test (DST) to assess cortisol secretion. "Single stick" cortisol values are si~ficantly confounded by the stress of venipuncture and the ultradian secretion pattern of K s hormone (Sachar et al 1982; Pepper and Krieger 1984). Furthermore, while there is overlap between DST nonsuppression and cortisol hypersecretion, these two neuroendocrme abnormalities do not necessarily coexist (Asnis et al 1981b, 1982; Holsboer et al 1984). The present study was designed to further evaluate NK cell activity in outpatients with depression and to determine whether depressed outpatients with plasma cortisol hypersecretion exhibit decreased NK cell activity compared to depressives and controls with normal cortisol secretion. In contrast to previous studies, cortisol secretion in this report was e,,aluated by a 1:00-4:00 PM plasma cortisol assessment, which gives an integrated plasma cortisol value that highly correlates with 24-hr cortisol secretion (Halbreich et al 1982).
Materials and M e t h o d s
Subjects Patients and controls were recruited from the same community sample through local • .~..a .-~A;*-=,,,advemsements.. , r k ,.. : ~ , ,j-,,,,,, , - , . . . . . . . -,,,,,,,o~,.,~=-.,.= h..o...~,;~ t,ou,.,,~, ..~.o-.o,/ ! ,9 w o r n , . I ~ newspa~r .1.,,, men) diagnosed with MDD using the Schedule for Affective Disorders ~.nd Schizophrenia (SADS) and Research Diagnostic Criteria (Endicott and Spitzer 1978; Spit~r et al 1978) and 21 paid controls (14 women and 7 men) participated in the study. All controls were screened using the SADS and were free from any evidence of a present or past psychiatric disorder ("never mentally ill"). The average age of the participants was 42.1 (SD -+ 14.8) for the MDD group and 36.7 (SD -+ 11.7) for the control group. Statistical comparison of the age (t = 1.4, df = 53, p > 0.16) and sex distribution (Fisher's exact test, p = 0.57) revealed no significant differences between the groups. All subjects were drug free for at least 14 clays and were medically healthy as determined by physical examination and routine laboratory tests including urine screening for drug abuse. Subjects meeting criteria (DSM-I 1I-R) for a drug or alcohol abuse disorder in the past year, or subjects taking steroids or other drugs known to affect the immune system within the past 6 months were excluded. The extracted Hamilton Depression Rating Scale (EH)
880
A.H. Miller et al
BIOL PSYCHL,xTR~ 1991;29:878-886
score for the depressed group at the time of study tanged from 11 to 41 with a mean of 20.5, SD _ 6.4 (Endicott et al 1981). The EH is a depression severity score derived from SADS questions that correspond to items on the Hamilton Depression Rating Scale (HDRS). EH scores are equivalent to HDRS scores and the two Lre highly correlated (Endicott et al 1981).
Plasma Cortisol Assessment All subjects underwent the 1:00--4:00 PM plasma cortisol assessment as described by Asnis et al (Asnis et al 1989). Blood samples of 5cc were collected every 30 rain for 4 hr (12:00-4:00 PM), and a plasma pool, made from equal alliquotsof half-hour samples from 1:00 to 4:00 PM, was utilizedas the assessment of basal cortisolsecretion. Subjects were subdivided into those with cortisol values ~> I l l~g/dl (hypersecretors) and those with cortisol values < I I l~g/dl (normosecretors) based on the work of Halbreich and colleagues who have used this value to discriminate cortisolhypersecrefion in psychiatric a:.d control populations (Halbreich et al 1986). Samples for plasma cortisol were analyzed in duplicate by a homologous double antibody radioimmunoassay (RIA) (Diagnostic Products Corporation, Los Angeles, CA). The intraassay and interassaycoefficientsof variation were 5.5% and 8.2% respectively.
Cytotoxicity Assays Whole blood (30 ml) was obtained at 12:30 PM on the day of the plasma cortisol assessment, and cell~mediated cytotoxicity was determined as previously described (Miller et al 1986). Briefly, peripheral blood lymphocytes were isolated on Ficoll-Hypaque cushions, purified by nylon column and cultured in RPMI 1640 medium with 15% fetal calf serum, 2 mm glutamine, 5 x 10 -5 mol/L 2-mercaptoethanol, 100 IU/ml penicillin, and 100 I~g/ml streptomycin (RPMI complete). One hundred microliters of viable lymphocytes were then added to 100 I~l of 5tCr-labeled K562 cells (2.5 x 104 viable cells/ml) in 96-well V-bottom microtiter plates (Nunc, Rosldlde, Denmark). The effector-to-target (E:T) ratios were 100:1, 50:1, 25:1, 12:1, and 6:1 with effector cell concentrations being 2.5 x 10 6 cells/ml at the 100:1 E:T ratio. After 3 hr at 37°C, 100 I~1 of supematant from triplicate samples were harvested, and the S~Cr radioactivity was determined in a Gamma Spectrophotometer (Model 1185, Searle Analytic, lnc, Des Plalnes, IL). Percentage of ~I.UILUAI~II.~ Wgi~ ~ I ~ U l a L ~ - M ILP~ U i ~ I U l l - ~ U l a l ~
~
l~rm
~Xl~nmunuu-~rm sponta-
neous)/(CPM maximum- CPM spontaneous)].
Statistical Analysis A repeated measures analysis of variance (ANOVA) was used to assess group differences in NK activity. Where indicated, contrasts between groups were made at specific E:T ratios using t-tests; Bonferonni correction was applied for multiple comparisons. The Fisher's exact test, the Student's t-test, and Pearson's correlation coefficients were used as indicated. All tests of significance were two-tailed with an alpha level set at 0.05. Results Although mean NK cell activity in depressed patients was no different than controls (F = 2.71; df = 1,53; p < 0. I l) (Figure l), there was a significant dose by group interac-
Depression, NK Activity, Cortisol Secretion
nK~t,vsvcmA'my
88 l
1991 ;29:STg-gl16
_u
Figure I. NK cell activity w ~ compared in a group of 34 non-
50
MDD
x
(n=34) u>
30
Control (n::~l)
zILl 2 0 U Q~
,., I
o
I
I
I
!
!
6:1
12.5:1
25:!
50:1
!00:!
21 controls. Percentage of cytotoxicity for each subject was detenmned at five separate effectorto-target (E:TA ratios using a standard 3-hr siChromium releaseassay. Mean percent cytoto~ity -4- SEM at each of the five E:T ratios is presented for the two groups.
EFFECTOR TO TARGET RATIO
tion ( F = 3.58; df = 4,50; p < 0.01) with contrasts revealing that depressed patients had greater NK cell activity than controls at the 25:1, 12.5:1, and 6:1 E:T ratios. Furthermore, as is shown in Figure 2, female depressive patients had significantly higher mean NK cell activity than female controls ( F = 4.91; df = 1,31; p < 0.034), whereas male depressive patients and male controls were no different in NK cell function ( F = 0.04; df = 1,20; p > 0.84). Using the 1:00-4:00 P M plasma cortisol assessment, depressed patients exhibited a
6O
T
Males
0
5O
40 3O
Controls ( n: 7 ) . / ~ '
_-/~jMfO (n=151
2O i#,,~
iu
I
0 5O
I
I
!
T,~/°
T
_Females MDD
4O
I
(n=lg)
-
/ - ~
T f-
30 20
_
w
I0 0
o ~ , -
~r'Controls__
(n= 14)
I
I
i
6:1
12.5:1 25:1
I
I
50:1
I00:1
EFFECTOR TO TARGET RATIO
Figure 2. NK cell activity at five separate effecmr-to-target (E:T) ratios was compared in male depressives versus male controls and female deoressives versus female controls. Mean percentage of cytotoxicity "4- SEM for all groups at each E:T ratio is presented.
882
BIOL PSYCHIATRY
A.H. Miller et al
1991;29:878-886
Table 1. Characteristics of MDD Cortisol Hypersecretors versus MDD Cortisol Nonnosecretors (Mean _+ SEM) MDD
Parameter Age Sex EH
Cortisol hypersecrelocs (n = 7)
Corlhoi nomtosecmtors (n = 27)
44.4 (7.0) 5 M, 2 F 19.9 (!.!)
41.6 (2.7) I0 M, 17 F 20.7 (!.4)
trend toward higher mean 1:00-4:00 PM plasma cortisol values than controls (9.1 Itg/dl SEM 0.77 versus 7.2 I~g/dl SEM 0.52; t -- 1.97; (If -- 5 2 . 1 ; p = 0.054). Seven of 34 depressives (20.6%) and 2 of 21 controls (9.5%) were cottisol hypersecretors using the criteria previously described. This frequency of cortisol hypersecretion was not different between the groups (Fisher's exact test, p = 0.46). No significant differences in age,
sex, and HDRS were noted between depressed cortisol hypersecretors and the depressed normosecretor group (Table 1). Comparison of NK cell activity in depressed cortisol hypersecretors, depressed cortisol normosecmtors, and control cortisol nonnosecretors revealed no statistically significant mean differences between the groups (F = 1.76; df = 2,50; p > 0.18) (Figure 3). The two control hypcrsecmtors were excluded from this analysis because the comparison of interest was between depressed hypcrsecretors and the depressed and control normosecretor groups. No significant correlations were observed between cortisol secretion and NK activity at any E:T ratio in either the depressed group (hypcrsecretors, normosecretors, or all depressives) or the control group or both groups combined. In addition, no significant correlations were noted between severity of depression (as determined by the EH) and NK activity or cortisol secretion in the depressed group. Finally, in male depressives (n = 15) there was a significant negative correlation (p -
_ ["1 Control (n=19) cortisol
BIOL PSYCHIATRY 1991;29:878-886
Depression, Natural Killer Cell Activity, and Cortisol Secretion Andrew H. Miller, Gregory M. Asnis, C Uriel Halbreich, and Allen J. Norin
stine Lackner,
Natural killer (NK) cell activity was evaluated in 34 ambulatory patients with Major Depressive Disorder (MDD) and 21 healthy controls. No mean differences between the groups were found. However, female depressives (n = 19) exhibited higher NK activity than female controls (n = 14). The relationship between cortisol secretion and NK activity was examined using an integrated cortisol value derived from multiple blood samples taken between 1.00 and 4.00 P~¢. This comprehensive assessment of cortisol secretion circumvents spurious ',single stick" cortisol values and provides a more accurate determination of hypercortisolemia than the dexamethasone suppression test. NK activity in depressives with cortisol hypersecretion (>11 Itgldl) (n = 7) was no different than NK activity ~ depressives and controls with normal cortisol secretion. Furthermore, there was no correlation between cortisol secretion and NK activity in any of the groups. These results indicate that decreased NK activity is not a consistent finding in MDD and cannot be predicted by the presence of hypercortisolemia in these patients.
Introduction Although five studies have reported decreased natural killer (NK) cell activity in patients with Major Depression (MD) (Irwin et al 1987, 1990a; Urch et al 1988; Nerozzi et al 1989; Kronfol et ai 1989), lowered NK cell function in MD has not been a consistent finding (Mohl et al 1987; Schleifer et al 1989). In a large study examining 91 patients d i a ~ n n ~ d w i t h ] ~ i n r Dept~,,ssive r~i~n,a,~. (MDD) and o t o.,,. and . . . . . o,.t,~a ,,,,.,.,,,,~o ne mean differences in NK cell activity were found between groups (Schleifer et al 1989). Furthermore. in this study, no mean differences were noted between depressives and controls in the lymphocyte proliferative response to three mitogens. Nevertheless. advancing age and increasing severity of depression were associated with lowered mitogeninduced proliferative responses in the depressed group. No such relationships were seen for NK cell activity. The authors concluded that altered immune function did not appear to be a specific biological correlate of depression but may occur in subgroups of depressed 'O'
~va
LI&¢I'W,~&
~¢ I
<~
=
OlkcA~llggllk~ll~dl
~lkBlllJIJclt.~
From the Mount Sinai School of Medicine (AHM, CL), New York, HY; the Albert Einstein College of Medicine (GMA), New York, NY; the State University of New York (UH), Buffalo, New York; and the State University of New York (AIN), Brooklyn, NY. Address reprint reo, w.sts to Andrew H. Miller, M.D., Box 1229 Annenberg 22-66, Mount Sinai School of Medicine, l Gustave L. Levy Place, New York, NY I0029. Received May 12, 1990, revised November 16, 1990.
© 1991 Society of Biological Psychiatry
0006-3223/91/$03.50
Depression, NK Activity, Cortisol ~cretion
em~. PSVCH~TaV
8"/9
199l ; 2 9 : 8 7 1 ~ ; 6
patients. Which subgroups of depressed individuals may exhibit alterations in NK activity remains unclear. One possibility may be those depressives who exhibit hypercortisolemia. Twenty percent to 55% of patients with MD exhibit c o . s o l hy-persecretion depending on a variety of factors including age. hospitalization status, and severity of depression (Asnis et al 1981a, 1982, 1989; Haibreich et al 1984; Asnis and l~mus 1987). In addition, NK cell function has been shown to be inhibited by corticosterot~ both in vitro ~ in vivo (Herberman 1982; Djeu et al 1979; Parillo and Fauci 1978; Miller et al 1987). and animal studies have indicated that corticosteroids are capable of mediating stress-induced alterations in cellular immune function of peripheral blood mononuclear cells (Rabin et al 1990). A number of studies have evaluated cortisol secretion and cellular immune function in the peripheral blood of depressed individuals versus control subjects (Syvalahti et. al !985: gronfol and House 1985; Exonfol et al 1985, 1986; Darko et al 1988a, 1988b; Nerozzi et al 1989; Schleifer et al 1989), and the results have t ~ e d to confirm a relationship between these two variables. Nevertheless, the majority of these studies have used either "single stick" measures of plasma cortiso! or the dexamethasone suppression test (DST) to assess cortisol secretion. "Single stick" cortisol values are si~ficantly confounded by the stress of venipuncture and the ultradian secretion pattern of K s hormone (Sachar et al 1982; Pepper and Krieger 1984). Furthermore, while there is overlap between DST nonsuppression and cortisol hypersecretion, these two neuroendocrme abnormalities do not necessarily coexist (Asnis et al 1981b, 1982; Holsboer et al 1984). The present study was designed to further evaluate NK cell activity in outpatients with depression and to determine whether depressed outpatients with plasma cortisol hypersecretion exhibit decreased NK cell activity compared to depressives and controls with normal cortisol secretion. In contrast to previous studies, cortisol secretion in this report was e,,aluated by a 1:00-4:00 PM plasma cortisol assessment, which gives an integrated plasma cortisol value that highly correlates with 24-hr cortisol secretion (Halbreich et al 1982).
Materials and M e t h o d s
Subjects Patients and controls were recruited from the same community sample through local • .~..a .-~A;*-=,,,advemsements.. , r k ,.. : ~ , ,j-,,,,,, , - , . . . . . . . -,,,,,,,o~,.,~=-.,.= h..o...~,;~ t,ou,.,,~, ..~.o-.o,/ ! ,9 w o r n , . I ~ newspa~r .1.,,, men) diagnosed with MDD using the Schedule for Affective Disorders ~.nd Schizophrenia (SADS) and Research Diagnostic Criteria (Endicott and Spitzer 1978; Spit~r et al 1978) and 21 paid controls (14 women and 7 men) participated in the study. All controls were screened using the SADS and were free from any evidence of a present or past psychiatric disorder ("never mentally ill"). The average age of the participants was 42.1 (SD -+ 14.8) for the MDD group and 36.7 (SD -+ 11.7) for the control group. Statistical comparison of the age (t = 1.4, df = 53, p > 0.16) and sex distribution (Fisher's exact test, p = 0.57) revealed no significant differences between the groups. All subjects were drug free for at least 14 clays and were medically healthy as determined by physical examination and routine laboratory tests including urine screening for drug abuse. Subjects meeting criteria (DSM-I 1I-R) for a drug or alcohol abuse disorder in the past year, or subjects taking steroids or other drugs known to affect the immune system within the past 6 months were excluded. The extracted Hamilton Depression Rating Scale (EH)
880
A.H. Miller et al
BIOL PSYCHL,xTR~ 1991;29:878-886
score for the depressed group at the time of study tanged from 11 to 41 with a mean of 20.5, SD _ 6.4 (Endicott et al 1981). The EH is a depression severity score derived from SADS questions that correspond to items on the Hamilton Depression Rating Scale (HDRS). EH scores are equivalent to HDRS scores and the two Lre highly correlated (Endicott et al 1981).
Plasma Cortisol Assessment All subjects underwent the 1:00--4:00 PM plasma cortisol assessment as described by Asnis et al (Asnis et al 1989). Blood samples of 5cc were collected every 30 rain for 4 hr (12:00-4:00 PM), and a plasma pool, made from equal alliquotsof half-hour samples from 1:00 to 4:00 PM, was utilizedas the assessment of basal cortisolsecretion. Subjects were subdivided into those with cortisol values ~> I l l~g/dl (hypersecretors) and those with cortisol values < I I l~g/dl (normosecretors) based on the work of Halbreich and colleagues who have used this value to discriminate cortisolhypersecrefion in psychiatric a:.d control populations (Halbreich et al 1986). Samples for plasma cortisol were analyzed in duplicate by a homologous double antibody radioimmunoassay (RIA) (Diagnostic Products Corporation, Los Angeles, CA). The intraassay and interassaycoefficientsof variation were 5.5% and 8.2% respectively.
Cytotoxicity Assays Whole blood (30 ml) was obtained at 12:30 PM on the day of the plasma cortisol assessment, and cell~mediated cytotoxicity was determined as previously described (Miller et al 1986). Briefly, peripheral blood lymphocytes were isolated on Ficoll-Hypaque cushions, purified by nylon column and cultured in RPMI 1640 medium with 15% fetal calf serum, 2 mm glutamine, 5 x 10 -5 mol/L 2-mercaptoethanol, 100 IU/ml penicillin, and 100 I~g/ml streptomycin (RPMI complete). One hundred microliters of viable lymphocytes were then added to 100 I~l of 5tCr-labeled K562 cells (2.5 x 104 viable cells/ml) in 96-well V-bottom microtiter plates (Nunc, Rosldlde, Denmark). The effector-to-target (E:T) ratios were 100:1, 50:1, 25:1, 12:1, and 6:1 with effector cell concentrations being 2.5 x 10 6 cells/ml at the 100:1 E:T ratio. After 3 hr at 37°C, 100 I~1 of supematant from triplicate samples were harvested, and the S~Cr radioactivity was determined in a Gamma Spectrophotometer (Model 1185, Searle Analytic, lnc, Des Plalnes, IL). Percentage of ~I.UILUAI~II.~ Wgi~ ~ I ~ U l a L ~ - M ILP~ U i ~ I U l l - ~ U l a l ~
~
l~rm
~Xl~nmunuu-~rm sponta-
neous)/(CPM maximum- CPM spontaneous)].
Statistical Analysis A repeated measures analysis of variance (ANOVA) was used to assess group differences in NK activity. Where indicated, contrasts between groups were made at specific E:T ratios using t-tests; Bonferonni correction was applied for multiple comparisons. The Fisher's exact test, the Student's t-test, and Pearson's correlation coefficients were used as indicated. All tests of significance were two-tailed with an alpha level set at 0.05. Results Although mean NK cell activity in depressed patients was no different than controls (F = 2.71; df = 1,53; p < 0. I l) (Figure l), there was a significant dose by group interac-
Depression, NK Activity, Cortisol Secretion
nK~t,vsvcmA'my
88 l
1991 ;29:STg-gl16
_u
Figure I. NK cell activity w ~ compared in a group of 34 non-
50
MDD
x
(n=34) u>
30
Control (n::~l)
zILl 2 0 U Q~
,., I
o
I
I
I
!
!
6:1
12.5:1
25:!
50:1
!00:!
21 controls. Percentage of cytotoxicity for each subject was detenmned at five separate effectorto-target (E:TA ratios using a standard 3-hr siChromium releaseassay. Mean percent cytoto~ity -4- SEM at each of the five E:T ratios is presented for the two groups.
EFFECTOR TO TARGET RATIO
tion ( F = 3.58; df = 4,50; p < 0.01) with contrasts revealing that depressed patients had greater NK cell activity than controls at the 25:1, 12.5:1, and 6:1 E:T ratios. Furthermore, as is shown in Figure 2, female depressive patients had significantly higher mean NK cell activity than female controls ( F = 4.91; df = 1,31; p < 0.034), whereas male depressive patients and male controls were no different in NK cell function ( F = 0.04; df = 1,20; p > 0.84). Using the 1:00-4:00 P M plasma cortisol assessment, depressed patients exhibited a
6O
T
Males
0
5O
40 3O
Controls ( n: 7 ) . / ~ '
_-/~jMfO (n=151
2O i#,,~
iu
I
0 5O
I
I
!
T,~/°
T
_Females MDD
4O
I
(n=lg)
-
/ - ~
T f-
30 20
_
w
I0 0
o ~ , -
~r'Controls__
(n= 14)
I
I
i
6:1
12.5:1 25:1
I
I
50:1
I00:1
EFFECTOR TO TARGET RATIO
Figure 2. NK cell activity at five separate effecmr-to-target (E:T) ratios was compared in male depressives versus male controls and female deoressives versus female controls. Mean percentage of cytotoxicity "4- SEM for all groups at each E:T ratio is presented.
882
BIOL PSYCHIATRY
A.H. Miller et al
1991;29:878-886
Table 1. Characteristics of MDD Cortisol Hypersecretors versus MDD Cortisol Nonnosecretors (Mean _+ SEM) MDD
Parameter Age Sex EH
Cortisol hypersecrelocs (n = 7)
Corlhoi nomtosecmtors (n = 27)
44.4 (7.0) 5 M, 2 F 19.9 (!.!)
41.6 (2.7) I0 M, 17 F 20.7 (!.4)
trend toward higher mean 1:00-4:00 PM plasma cortisol values than controls (9.1 Itg/dl SEM 0.77 versus 7.2 I~g/dl SEM 0.52; t -- 1.97; (If -- 5 2 . 1 ; p = 0.054). Seven of 34 depressives (20.6%) and 2 of 21 controls (9.5%) were cottisol hypersecretors using the criteria previously described. This frequency of cortisol hypersecretion was not different between the groups (Fisher's exact test, p = 0.46). No significant differences in age,
sex, and HDRS were noted between depressed cortisol hypersecretors and the depressed normosecretor group (Table 1). Comparison of NK cell activity in depressed cortisol hypersecretors, depressed cortisol normosecmtors, and control cortisol nonnosecretors revealed no statistically significant mean differences between the groups (F = 1.76; df = 2,50; p > 0.18) (Figure 3). The two control hypcrsecmtors were excluded from this analysis because the comparison of interest was between depressed hypcrsecretors and the depressed and control normosecretor groups. No significant correlations were observed between cortisol secretion and NK activity at any E:T ratio in either the depressed group (hypcrsecretors, normosecretors, or all depressives) or the control group or both groups combined. In addition, no significant correlations were noted between severity of depression (as determined by the EH) and NK activity or cortisol secretion in the depressed group. Finally, in male depressives (n = 15) there was a significant negative correlation (p -
_ ["1 Control (n=19) cortisol
