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Serial dexamethasone suppression tests (DST) in recently hospitalized children
Serial Dexamethasone Suppression Tests (DST) in Recently Hospitalized Children Charles D. Casat, Deborah Pearson, Javier Ruiz-Nazario, and Howard Rhoades K e y W o r d s : Depression, children, DST, altered DEX metabolism
Introduction We have previously reported a metaanalysis of eight studies of the dexamethasone suppression test (DST) in children (Casat et al 1989). Fifty-five of 79 child subjects (69.6%) with major depressive disorder (MDD) and 47.1% of adolescent MDD subjects were nonsnppressors. As a comparison, Arana et al (1985) reported 44.5% DST nonsuppression in adult MDD subjects. Further, the metaanalysis showed more inpatient (81.7%) than outpatient (31.6%) MDD children were nonsuppressors (p < 0.0000). We became interested in understanding the apparent variance between DST results in the children, and those among adolescents and adults with MDD. To investigate hospitalization as a stressor impacting corfisol production in acutely psychiatrically disturbed children, we measured postdexamethasone cortisol and concomitant dexamethasone (DEX) levels on Day 2 and Day 7 following admission. We hypothesized increased DEX resistance and DST nonsuppression would be seen in both depressed (DEPR) and nondepressed (NDEPR) groups at Day 2 after hospitalization, but that any stress effect would diminish by Day 7, with only the DEPR continuing to show nonsuppression at
I~a,.t 7
Methods Subjects Children ages 7-12 years admitted on an emergency basis to a publically funded children's inpatient psychiatric service were eligible for study enrollment if they (1) met DSM III-R criteria for major depressive disorder, dysthymic disorder, bipolar disorder- depressed, overanxious disorder, separation anxiety disFromthe DivisionofChildandAdolescentPsychiatry,DepartmentofPsychiatryand BehavioralSciences.UniversityofTexas,Houston,TX. Reprintsnot available. ReceivedNovember17. 1992;revisedDecember14.1993. © 1994SocietyofBiologicalPsychial~j
order, conduct disorder, oppositional defiant disorder, or attention ~ficit h~,~eractivity disorder;, (2) had an IQ ~> 80;, (3) were in good physical health; (4) had no significant recem weight loss (>4.4 pounds within 2 weeks of enrollment); (5) had not used alcohol, illicit drugs, or psychotropic medications in the past 2 weeks. Female subjects had to be prernenarchal. Informed consents (parents) and assents (child) were obtained prior to enrollment. Twenty subjects were enrolled (13 boys and 7 girls). These were separated into a depressed group (DEPR) and a nondepressed group (NDEPR) for between-groups analysis. Among the DEPR (n = 11), there were 6 boys and 5 girls, whereas in the NDEPR (n = 9) there were 7 boys and 2 girls. There were no differences in the sex or age of the groups (see Table !).
Hospital Treatment All subjects received similar evaluations and milieu interventions during the first 7 days, and none was placed on psychotropic medications.
Assessments Each child was interviewed by the Principal Investigator at hospital Day 7, using the Schedule of Affective Disorders and Schizophrenia, children's epidemiologic version (K-SADS-E), (Chambers et al 1985). Diagnoses were rendered from the" KSADS using the DSM-III-R nomenclature. Subjects completed the Children's Depression Inventory (CDI) on Day 2 and again on Day 7 of the study.
Cortisol and DEX Measurements Blood was drawn at 8 AM on Days I and day 6 for baseline plasma cortisol assay. A dose of 0.5 mg of dexamethasone was administered po at ! 1 PM on Day 1 and Day 6. Blood was drawn at 8 AM and 4 PM on Days 2 and 7 for determination of plasma DEX and cortisol measurements. All blood samples were processed imme0006-3223/94/$07.00
BIOk[~¥CHIATRY 1994;36:~d5
BriefRepmts
Table 1. Between-Groups Comparison ofCDI. Cortisol, and DEX Values
Sex distrilmtion: Age:
Depressed (DEPR) group (n = ! I)
Nondei~essed(NDEPR) group (n =9)
6 boys, 5 girls 10.1 --- 1.4 (Mean z SEM) 18.73 -+ 3.41 (Range 7-45) 17.82 ± 2.72
7 boys, 2 girls 10.8 Z 1.7 (Mean - SEM) 12.56 -+ 3.77 (Range 4-34) 9.33 Z 3.02 (Range 1-28)
CDI Score: Day 2 CDI Score: Day 7 (Range 3-34) BaselinecortisoL/.tg/dl: Day 1,8AM 13.91 - 1.45 Day 6, 8 AM 10.85 Z .86 Post-alexcortisol,/zg/di: Day 2,SAM 2.30 ± 1.23 Day 2,4PM 2.21 -+ 1.17 Day 7, 8 AM 1.87 Z .87 Day 7, 4 PM 1.67 _..T..69 Dex, ng/ml: Day 2,8 AM 73.10 -- 6.84 Day2,4PM 17.46 Z 2.41 Day 7, 8 AM 76.13 +--8.26 Day7,4PM 21.82 -+ 3.36 Maineffect ofdex levelon cortisoiresponse: l>ay2, 8 AM t =--0.30 Day 2,4PM t =-0.56 Day 7, 8 AM t= -0.55 Day 7,4 PM t =-0.64
X: -- !, 17
p-- 0.279 NS
t=(-).99 (f-ratio) r-(IA8) = 1.47
NS
p =0~241NS
F(LI8)=4.33
p=0.052
17.27 -----1.60 14.89 ----.95
F(I,18)=2.41
p=O.138NS p = 0.006
5.07 _ 6.59 6.59--1.30 3.01 + .96 4.13 Z .76
F(I,18)=2.26 F(I,18)=6.28 F(l,18)= .77 F(I, 18) = 5.74
p=O.15ONS
43.8t Z 7.56 8.98 - P_66 56.82 -+9.13 9.91 ..4-3.71
F(I,18)--8.25 F(l,18) =5.58 !:(!,18)=2.46 F(1,18)=5.64
p=O.OlO p=0.030 p=0.134NS p=O.028
F(I,18) = 1.77 F(I,18) =8.24 [:(1,18) = 7.69 F(l,18)= 12.22
p =0.200 NS p =0.010 p =0.013
F( !, 18) = 9.8"/
p=0.022 p =0.391 NS p = 0.028
p=O.O03
diately and frozen until batched for assay. DEX was assayed by radioimmunoassay procedure (Lo et al 1989). Cortisol was assayed by radioimmunoassay procedure.
4 PM on Day 2 (/7 = 0.022), and again at 4 PM on Day 7 (p < 0.028) (see Table I).
Results
DEX for the DEPR was significantly greater than the NDEPR at both 8 AMon Day 2 (p ~-.0.010), and 4 PM onDay 2 (p = 0.030), and at 4 PMon Day 7 (p = 0,029) (see Table 1).
CDI Scores At Day 2, there was no difference in CDI scores between the DEPR and NDEPR, whereas by Day 7, the scores for DEPR were significantly higher than the NDEPR (F = 4.33, p = 0.052) (see Table 1). The CDI scores for the DEPR remained relatively unchanged between Days 2 and day 7 (t = 0.20, dr= 1, NS), whereas those in the NDEPR dropped significantly(t = 2.89, df = 1, p = 0.02).
DST Results The ~>5.0 Ixg/dl criterion fer nonsuppression was used. (Pfeffer et al 1989). At Days 2, 3 the DEPR were among the nonsuppressors; 5 of the NDEPR were among the nonsuppressors (X2= 1.65, df= 1, p = 0.199 NS). At Day 7, there were 2 nonsuppressors among the DEPR, and 3 of the NDEPR were among the nonsuppressors (X2= 0.606, df = l , p = 0.436 NS). The total number of DST nonsuppressots between Days 2 and 7 decreased from 8 to 5 subjects, but was not significant (X2= 1.03, p = 0.311, NS).
Cortisol Levels Cortisol levels were significantly higher for the NDEPR than the DEPR at baseline on Day 6 (p = 0.006), and postdexamethasone at
Dexamethasone Levels
DEX/Cortisol Main Interaction An inverse correlation was noted between DEX and cortisoi values, independent of diagnostic group (see Table 1). This relationship was significant, with the DEX levels sharing in common a high proportion of the variance with the postDEX cortisol values except for 8 AMon Day 2.
Discussion Although the current DST results are inconclusive when taken by themselves, this finding is in keeping with results of recent studies by Naylor et al (1990), and of Birmaher et al (1992), who found low DST sensitivity and specificity among child inpatient subjects. Coccaro et al 0984) reported DST nonsuppression among adults with MDD was greater at Day 2 after admission than when tested at Day 4 or later. Although in the current study there was a net drop in total nonsuppressors from eight subjects to five from Day 2 to Day 7, the change was not significant, and thus the hypothesis of a stress effect on DST results in child subjects due to hospitalization was not confirmed. The CDI scores among the
Brief Reports
DEPR remmned unchanged at Day 7 from Day 2, paratlefing CDI scores reported by Fristad et el (1991) among inpatient child MDD subjects, while the CDI scores from Day 2 to Day 7 in the NDEPR decreased. This finding in the NDEPR may be artifact or a decrease in transient dysphoria, as the CDI has a low specificity and reflects negative affecfivity as well as depression (Finch et al 1989). Conclusions in the current study are fimited by the number of subjects involved. It does not address the issue of comod~idity because of the small number of subjects. The influence of comorbidity among children with MDD or ADHD has been noted in several studies (Steingard et at 1990: Jensen et at 1993) but has not been fully elaborated. Further investigations should also employ measures of parental pathology, family turmoil, and perceived
atot,~cttlA~tv
205
slless of hospitalization as po~ible e n ~ ~ correlates for high conisol levels. This study extends the ~ ofan inverse correlation ~ plasma cortisol and concomitant DEX levels in children and independent of diagnostic category (Naykx-et at t990; B ~ e ~ a11992;Guthrie 1991).Webelievethisisthe f i r s t r e p ~ o f ~ tendy higher serum DEX leveh among ~ ~ ch~dren. This finding, suggesting an ~ of DEX metabeAi~m, has been repogted previo~ly in adult MDD subjects by GtahrJe e~ at ( ! 992). Guthrie's group susgested that a longer DEX haft-life in individuals during a ~ i v e episode might rewesem a state marker for depression. This work needs to be e x ~ in c,hiki~'n to test this preliminary observation.
References American Psychiatric Association ( 1987): Diagnostic and Statistical Manual for Mental Disorders- Revised. Washington, DC: American Psychiatric Press. Arana GW, Baslsessarini RJ, Omsteen M (i 985): The dexamethasone suppression test for diagnosis and prognosis in psychiatry. Arch Gen Psychiatry 42: ! 193-1204. Birmaher B, Ryan ND, Dahl R, et at (1992); Dexamethasone suppression test m children with major depressive disorder. J Am Acad ChildAdolesc Psychiatry. 31:291-297. Casat CD, Arana GW, Powell K (1989): The DST in children and adolescents with major depressive disorder. Am J Psychiatry 146: 503-507. Chambers WJ, Puig-Antich J, Hirsch M, et at (1985): The assessmere of affective disorders in children and adolescents by a semistructured interview. Arch Gen Psychiatry 42:696--702. Coccaro EF, Prudic J, Rothpearl A, Nurnberg HG (1984): Effect of hospital admission on DST results. Am J Psychiatry 141:982985. Finch AJ Jr, Lipovsky JA, Casat CD (1989): Anxiety and depression in children and adolescents: Negative affectivity or separate constructs? In Kendall PC, Watson D (eds), Anxiety and Depression: Distinctive and Overlapping Features. Orlando, FL: Academic Press. Fristad MA, Weller RA, Weller EB, Teare M, Preskom SH (1991 ): Comparison of the parent and child versions of the Children's Depression Inventory (CDI). Ann Clin Psychiatry 3:341-346.
Guthrie S (199 i): The impact ofdexame~u3~e ~ o k i n e t i c s on the DST: A Review. Psychopharmacol Bull 27:565-576. Guthrie SK, Heidt M, Pande A+ Gmnhaus L, Haskett RF, Har~haran M 0992): A longitudinal evaluation of dexamethasone pharmacokinetics in depressed ~ t s and nonnat controls. J Clin Psyehopharmacol ! 2:191-I96. Jensen PS, Sbervette RE HI, Xenakis SN, Richiers J (1993): Anxiety and depressive disorders in attention deficit disorder with hyperactivity: New findings. Am J Psychiatry 150(8):12031209. Lo EES, Huttinot G, Fein M, Cooper TB (1989): Direct radioimmunoassay for plasma dexamethasone with sensitivity at the picogram level. J Pharmacol Sci 78:1044-1046. Naylor MW, Greden JF, Alessi NE (1990): Plasma dexamcthasone levels in children given the dexamethasone suppression test. Biol Psychiatry 27:592-600. Nelson WM, Pofitano PM, Finch AJ, Wendel N, Mayhall C (1987): Children's Depression Inventory: Normative data and utifity with emotionally disturbed children. J Am Acad Child Adolesc Psychiatry. 26:43--48. Pfeffer CR, Stokes P, Weiner A, et al (1989): Psychopathology and plasma corfisol responses to dexamethasone in prepubertal psychiatric inpatients. Biol Psychiatry 26:677--689. Steingard R, Biederman J, Keenan K, Moore C (1990): Comorbidity in the interpretation of dexamethasone suppression tests in children: A review and report. Biol Psychiatry 28:193-202.
Introduction We have previously reported a metaanalysis of eight studies of the dexamethasone suppression test (DST) in children (Casat et al 1989). Fifty-five of 79 child subjects (69.6%) with major depressive disorder (MDD) and 47.1% of adolescent MDD subjects were nonsnppressors. As a comparison, Arana et al (1985) reported 44.5% DST nonsuppression in adult MDD subjects. Further, the metaanalysis showed more inpatient (81.7%) than outpatient (31.6%) MDD children were nonsuppressors (p < 0.0000). We became interested in understanding the apparent variance between DST results in the children, and those among adolescents and adults with MDD. To investigate hospitalization as a stressor impacting corfisol production in acutely psychiatrically disturbed children, we measured postdexamethasone cortisol and concomitant dexamethasone (DEX) levels on Day 2 and Day 7 following admission. We hypothesized increased DEX resistance and DST nonsuppression would be seen in both depressed (DEPR) and nondepressed (NDEPR) groups at Day 2 after hospitalization, but that any stress effect would diminish by Day 7, with only the DEPR continuing to show nonsuppression at
I~a,.t 7
Methods Subjects Children ages 7-12 years admitted on an emergency basis to a publically funded children's inpatient psychiatric service were eligible for study enrollment if they (1) met DSM III-R criteria for major depressive disorder, dysthymic disorder, bipolar disorder- depressed, overanxious disorder, separation anxiety disFromthe DivisionofChildandAdolescentPsychiatry,DepartmentofPsychiatryand BehavioralSciences.UniversityofTexas,Houston,TX. Reprintsnot available. ReceivedNovember17. 1992;revisedDecember14.1993. © 1994SocietyofBiologicalPsychial~j
order, conduct disorder, oppositional defiant disorder, or attention ~ficit h~,~eractivity disorder;, (2) had an IQ ~> 80;, (3) were in good physical health; (4) had no significant recem weight loss (>4.4 pounds within 2 weeks of enrollment); (5) had not used alcohol, illicit drugs, or psychotropic medications in the past 2 weeks. Female subjects had to be prernenarchal. Informed consents (parents) and assents (child) were obtained prior to enrollment. Twenty subjects were enrolled (13 boys and 7 girls). These were separated into a depressed group (DEPR) and a nondepressed group (NDEPR) for between-groups analysis. Among the DEPR (n = 11), there were 6 boys and 5 girls, whereas in the NDEPR (n = 9) there were 7 boys and 2 girls. There were no differences in the sex or age of the groups (see Table !).
Hospital Treatment All subjects received similar evaluations and milieu interventions during the first 7 days, and none was placed on psychotropic medications.
Assessments Each child was interviewed by the Principal Investigator at hospital Day 7, using the Schedule of Affective Disorders and Schizophrenia, children's epidemiologic version (K-SADS-E), (Chambers et al 1985). Diagnoses were rendered from the" KSADS using the DSM-III-R nomenclature. Subjects completed the Children's Depression Inventory (CDI) on Day 2 and again on Day 7 of the study.
Cortisol and DEX Measurements Blood was drawn at 8 AM on Days I and day 6 for baseline plasma cortisol assay. A dose of 0.5 mg of dexamethasone was administered po at ! 1 PM on Day 1 and Day 6. Blood was drawn at 8 AM and 4 PM on Days 2 and 7 for determination of plasma DEX and cortisol measurements. All blood samples were processed imme0006-3223/94/$07.00
BIOk[~¥CHIATRY 1994;36:~d5
BriefRepmts
Table 1. Between-Groups Comparison ofCDI. Cortisol, and DEX Values
Sex distrilmtion: Age:
Depressed (DEPR) group (n = ! I)
Nondei~essed(NDEPR) group (n =9)
6 boys, 5 girls 10.1 --- 1.4 (Mean z SEM) 18.73 -+ 3.41 (Range 7-45) 17.82 ± 2.72
7 boys, 2 girls 10.8 Z 1.7 (Mean - SEM) 12.56 -+ 3.77 (Range 4-34) 9.33 Z 3.02 (Range 1-28)
CDI Score: Day 2 CDI Score: Day 7 (Range 3-34) BaselinecortisoL/.tg/dl: Day 1,8AM 13.91 - 1.45 Day 6, 8 AM 10.85 Z .86 Post-alexcortisol,/zg/di: Day 2,SAM 2.30 ± 1.23 Day 2,4PM 2.21 -+ 1.17 Day 7, 8 AM 1.87 Z .87 Day 7, 4 PM 1.67 _..T..69 Dex, ng/ml: Day 2,8 AM 73.10 -- 6.84 Day2,4PM 17.46 Z 2.41 Day 7, 8 AM 76.13 +--8.26 Day7,4PM 21.82 -+ 3.36 Maineffect ofdex levelon cortisoiresponse: l>ay2, 8 AM t =--0.30 Day 2,4PM t =-0.56 Day 7, 8 AM t= -0.55 Day 7,4 PM t =-0.64
X: -- !, 17
p-- 0.279 NS
t=(-).99 (f-ratio) r-(IA8) = 1.47
NS
p =0~241NS
F(LI8)=4.33
p=0.052
17.27 -----1.60 14.89 ----.95
F(I,18)=2.41
p=O.138NS p = 0.006
5.07 _ 6.59 6.59--1.30 3.01 + .96 4.13 Z .76
F(I,18)=2.26 F(I,18)=6.28 F(l,18)= .77 F(I, 18) = 5.74
p=O.15ONS
43.8t Z 7.56 8.98 - P_66 56.82 -+9.13 9.91 ..4-3.71
F(I,18)--8.25 F(l,18) =5.58 !:(!,18)=2.46 F(1,18)=5.64
p=O.OlO p=0.030 p=0.134NS p=O.028
F(I,18) = 1.77 F(I,18) =8.24 [:(1,18) = 7.69 F(l,18)= 12.22
p =0.200 NS p =0.010 p =0.013
F( !, 18) = 9.8"/
p=0.022 p =0.391 NS p = 0.028
p=O.O03
diately and frozen until batched for assay. DEX was assayed by radioimmunoassay procedure (Lo et al 1989). Cortisol was assayed by radioimmunoassay procedure.
4 PM on Day 2 (/7 = 0.022), and again at 4 PM on Day 7 (p < 0.028) (see Table I).
Results
DEX for the DEPR was significantly greater than the NDEPR at both 8 AMon Day 2 (p ~-.0.010), and 4 PM onDay 2 (p = 0.030), and at 4 PMon Day 7 (p = 0,029) (see Table 1).
CDI Scores At Day 2, there was no difference in CDI scores between the DEPR and NDEPR, whereas by Day 7, the scores for DEPR were significantly higher than the NDEPR (F = 4.33, p = 0.052) (see Table 1). The CDI scores for the DEPR remained relatively unchanged between Days 2 and day 7 (t = 0.20, dr= 1, NS), whereas those in the NDEPR dropped significantly(t = 2.89, df = 1, p = 0.02).
DST Results The ~>5.0 Ixg/dl criterion fer nonsuppression was used. (Pfeffer et al 1989). At Days 2, 3 the DEPR were among the nonsuppressors; 5 of the NDEPR were among the nonsuppressors (X2= 1.65, df= 1, p = 0.199 NS). At Day 7, there were 2 nonsuppressors among the DEPR, and 3 of the NDEPR were among the nonsuppressors (X2= 0.606, df = l , p = 0.436 NS). The total number of DST nonsuppressots between Days 2 and 7 decreased from 8 to 5 subjects, but was not significant (X2= 1.03, p = 0.311, NS).
Cortisol Levels Cortisol levels were significantly higher for the NDEPR than the DEPR at baseline on Day 6 (p = 0.006), and postdexamethasone at
Dexamethasone Levels
DEX/Cortisol Main Interaction An inverse correlation was noted between DEX and cortisoi values, independent of diagnostic group (see Table 1). This relationship was significant, with the DEX levels sharing in common a high proportion of the variance with the postDEX cortisol values except for 8 AMon Day 2.
Discussion Although the current DST results are inconclusive when taken by themselves, this finding is in keeping with results of recent studies by Naylor et al (1990), and of Birmaher et al (1992), who found low DST sensitivity and specificity among child inpatient subjects. Coccaro et al 0984) reported DST nonsuppression among adults with MDD was greater at Day 2 after admission than when tested at Day 4 or later. Although in the current study there was a net drop in total nonsuppressors from eight subjects to five from Day 2 to Day 7, the change was not significant, and thus the hypothesis of a stress effect on DST results in child subjects due to hospitalization was not confirmed. The CDI scores among the
Brief Reports
DEPR remmned unchanged at Day 7 from Day 2, paratlefing CDI scores reported by Fristad et el (1991) among inpatient child MDD subjects, while the CDI scores from Day 2 to Day 7 in the NDEPR decreased. This finding in the NDEPR may be artifact or a decrease in transient dysphoria, as the CDI has a low specificity and reflects negative affecfivity as well as depression (Finch et al 1989). Conclusions in the current study are fimited by the number of subjects involved. It does not address the issue of comod~idity because of the small number of subjects. The influence of comorbidity among children with MDD or ADHD has been noted in several studies (Steingard et at 1990: Jensen et at 1993) but has not been fully elaborated. Further investigations should also employ measures of parental pathology, family turmoil, and perceived
atot,~cttlA~tv
205
slless of hospitalization as po~ible e n ~ ~ correlates for high conisol levels. This study extends the ~ ofan inverse correlation ~ plasma cortisol and concomitant DEX levels in children and independent of diagnostic category (Naykx-et at t990; B ~ e ~ a11992;Guthrie 1991).Webelievethisisthe f i r s t r e p ~ o f ~ tendy higher serum DEX leveh among ~ ~ ch~dren. This finding, suggesting an ~ of DEX metabeAi~m, has been repogted previo~ly in adult MDD subjects by GtahrJe e~ at ( ! 992). Guthrie's group susgested that a longer DEX haft-life in individuals during a ~ i v e episode might rewesem a state marker for depression. This work needs to be e x ~ in c,hiki~'n to test this preliminary observation.
References American Psychiatric Association ( 1987): Diagnostic and Statistical Manual for Mental Disorders- Revised. Washington, DC: American Psychiatric Press. Arana GW, Baslsessarini RJ, Omsteen M (i 985): The dexamethasone suppression test for diagnosis and prognosis in psychiatry. Arch Gen Psychiatry 42: ! 193-1204. Birmaher B, Ryan ND, Dahl R, et at (1992); Dexamethasone suppression test m children with major depressive disorder. J Am Acad ChildAdolesc Psychiatry. 31:291-297. Casat CD, Arana GW, Powell K (1989): The DST in children and adolescents with major depressive disorder. Am J Psychiatry 146: 503-507. Chambers WJ, Puig-Antich J, Hirsch M, et at (1985): The assessmere of affective disorders in children and adolescents by a semistructured interview. Arch Gen Psychiatry 42:696--702. Coccaro EF, Prudic J, Rothpearl A, Nurnberg HG (1984): Effect of hospital admission on DST results. Am J Psychiatry 141:982985. Finch AJ Jr, Lipovsky JA, Casat CD (1989): Anxiety and depression in children and adolescents: Negative affectivity or separate constructs? In Kendall PC, Watson D (eds), Anxiety and Depression: Distinctive and Overlapping Features. Orlando, FL: Academic Press. Fristad MA, Weller RA, Weller EB, Teare M, Preskom SH (1991 ): Comparison of the parent and child versions of the Children's Depression Inventory (CDI). Ann Clin Psychiatry 3:341-346.
Guthrie S (199 i): The impact ofdexame~u3~e ~ o k i n e t i c s on the DST: A Review. Psychopharmacol Bull 27:565-576. Guthrie SK, Heidt M, Pande A+ Gmnhaus L, Haskett RF, Har~haran M 0992): A longitudinal evaluation of dexamethasone pharmacokinetics in depressed ~ t s and nonnat controls. J Clin Psyehopharmacol ! 2:191-I96. Jensen PS, Sbervette RE HI, Xenakis SN, Richiers J (1993): Anxiety and depressive disorders in attention deficit disorder with hyperactivity: New findings. Am J Psychiatry 150(8):12031209. Lo EES, Huttinot G, Fein M, Cooper TB (1989): Direct radioimmunoassay for plasma dexamethasone with sensitivity at the picogram level. J Pharmacol Sci 78:1044-1046. Naylor MW, Greden JF, Alessi NE (1990): Plasma dexamcthasone levels in children given the dexamethasone suppression test. Biol Psychiatry 27:592-600. Nelson WM, Pofitano PM, Finch AJ, Wendel N, Mayhall C (1987): Children's Depression Inventory: Normative data and utifity with emotionally disturbed children. J Am Acad Child Adolesc Psychiatry. 26:43--48. Pfeffer CR, Stokes P, Weiner A, et al (1989): Psychopathology and plasma corfisol responses to dexamethasone in prepubertal psychiatric inpatients. Biol Psychiatry 26:677--689. Steingard R, Biederman J, Keenan K, Moore C (1990): Comorbidity in the interpretation of dexamethasone suppression tests in children: A review and report. Biol Psychiatry 28:193-202.