Table 2.
Studies of basal cortisol functioning in children and adolescents
| Study | Sample | MDD | Control | MDD measure | Collection method/time | Nighttime cortisol | Daytime and/or total cortisol |
|---|---|---|---|---|---|---|---|
| Pfeffer et al. 1989 | Inpatient children | 20 MDD (unknown comorbidities) | 19 DD 9 SZ-S 3 Neither | Dx assigned according to DSM-III criteria based on 2 independent K-SADS-P with parents and children | Venipuncture @ 8 am, 4, and 11 pm | Equivalent | Equivalent |
| Casat et al. (1994) | Inpatient children | 11 MDD (unknown comorbidities) | 9 PC | Dx assigned according to DSM-III criteria based on K-SADS-E | Venipuncture @ 8 AM on two separate days | N/A | Lower |
| Birmaher et al. (1996) | Both inpatient and outpatient children | 34 MDD (unknown comorbidities) | 22 NC | Dx assigned according to RDC based on parent and child K-SADS-P and K-SADS-E | Indwelling venous catheter; samples taken 30, 15, 0 min before 9 am CRH infusion | N/A | Equivalent |
| Kaufman et al. (1997b) | Both inpatient and outpatient children | 13 MDD abused 13 MDD non | 13 NC | Dx assigned according to RDC based on 2 independent K-SADS | Indwelling venous catheter: samples taken at 30, 15, and 0 min pre- CRH infusion | N/A | Equivalent |
| Birmaher et al. (1992b) | Outpatient children | 23 MDD (15 endogenous, 6 psychotic, 18 suicidal) | 13 PC 9 NC | Dx assigned according to DSM-III (PC) or RDC criteria (MDD) based on 2 independent parent and child KSADS-P | Indwelling catheter: 24 hourly samples beginning 9 PM | Equivalent | Equivalent |
| Feder et al. (2004) | Outpatient children | 76 MDD (unknown comorbidities) | 31 ANX 17 NC | Dx assigned according to RDC criteria based on 2 independent K-SADS-P | Indwelling venous catheter: hourly blood samples collected over 24-hr period | Equivalent | Equivalent |
| Luby et al. (2003) | Outpatient preschoolers | 55 MDD (unknown comorbidities) | 43 PC 57 NC | Parent DISC (modified to be developmentally appropriate) | Saliva samples collected on 3 consecutive nights | Equivalent | N/A |
| Forbes et al. (2006) | Outpatient children and adolescents | 116 MDD (unknown comorbidities) | 32 ANX 76 NC | Dx assigned by case conference consensus based on K-SADS-PL | Indwelling venous catheter: daytime = 40, 20, and 0 min before CRH infusion; nighttime = every 20 min beginning 2 h before individual bedtime | Higher than NC | N/A |
| Puig-Antich et al. (1989) | Outpatient children | 45 MDD (unknown comorbidities) | 20 PC 8 NC | Dx assigned according to RDC criteria based on 2 independent K-SADS-Ps | Indwelling venous catheter: samples every 20 min for 24 h | Equivalent | Equivalent |
| Doherty et al. (1986) | Inpatient children and adolescents | 43 MDD (significant comorbidity) | 29 PC | Dx assigned according to DSM-III criteria following “Standard clinical assessment” | Venipuncture @ 8 am and 11 pm. | Equivalent | Equivalent |
| Goodyer et al. (1996) | Outpatient children and adolescents | 82 MDD (unknown comorbidities) | 11 PC 40 NC | Dx assigned according to DSM-III-R criteria based on K-SADS-P | Salivary cortisol samples at 8 AM, 12 PM, 8 PM over 2 consecutive days | Higher than both PC, NC | Equivalent |
| Extein et al. (1982) | Inpatient adolescents | 15 MDD (unknown comorbidities) | 12 PC | Dx assigned according to DSM-III criteria based on semistructured interviews | Venipuncture @ 4 pm, midnight, and 8 am. | Equivalent | Equivalent |
| Kutcher et al. (1991) | Inpatients adolescents | 12 MDD (unknown comorbidities) | 12 NC | Dx assigned according to DSM-III-R criteria based on K-SADS | Indwelling venous catheter: samples at 10 PM, 12 AM, 1, 2, 3, 4, and 6 AM | Equivalent | Equivalent |
| Dahl et al. (1991) | Inpatient and outpatient adolescents | 27 MDD (“significant comorbidity”) | 32 NC | Dx assigned according to adult RDC criteria based on 2 independent K-SADS-Ps | Indwelling venous catheter: blood draws every 20 min for 24 h (starting 8:30 AM) | Higher | Equivalent |
| Rao et al. (2008) | Outpatient adolescents | 30 MDD (unknown comorbidities) | 25 NC | Dx assigned according to DSM-IV criteria based on adolescent and parent K-SADS-PL | Saliva samples collected at 30 min intervals for 2 h (i.e., 5 samples) | N/A | Equivalent |
| Dahl et al. (1989) | Outpatient adolescents | 48 MDD (unknown comorbidities) | 40 NC | Dx assigned according to adult RDC criteria based on 2 independent K-SADS-Ps | Indwelling venous catheter: blood samples every 20 min for 24 h | Equivalent | Equivalent |
| Rao and Poland (2008) | Outpatient adolescents | 16 MDD (unknown comorbidities) | 16 NC | Dx assigned according to DSM-IV criteria based on adolescent and parent K-SADS-PL | Nocturnal urinary free cortisol (10:30 pm and 7 am samples) | Higher | N/A |
| Mathew et al. (2003) a | Outpatient adolescents, in 10 year follow-up study | 48 MDD at Time 1; 56 MDD at Time 2 (15 with comorbid anxiety disorder) | 21 NC | Dx assigned according to SADS-LA according to best estimate procedure | Indwelling venous catheter; blood samples every 20 min for 24 h (starting in the A.M.) | Equivalent, but LOWER in subsequently suicidal outpatients | Equivalent, but HIGHER in subsequently suicidal outpatients |
| Goodyer et al. (2003) b | Outpatient adolescents, in 2 year follow-up study | 30 MDD (19 RMD, 11 PMD) | 30 NC (high risk, never depressed) | Dx assigned according to DSM-IV criteria based on the Kiddie-SADs patient version | Salivary cortisol samples at 8 A.M. and 8 P.M. over 4 consecutive days | Equivalent | Equivalent, but higher morning cortisol:DHEA ratio in PMD |
| Adam et al. (2010) c | Outpatient adolescents, in 1 year follow-up study | 40 past MDD and 16 current MDD at Time 1; 18 MDD at Time 2 (9 recurrences, 9 new cases); 20 with subclinical MDD at Time 2. | 192 NC (over-sampled for high neuroticism) | Dx assigned according to the DSM-IV (SCID) | Salivary cortisol samples gathered 6 times per day over 3 consecutive weekdays: at wake-up, 40 min after waking, at 3, 8, and 12 h post-awakening, and at bedtime. | Equivalent | Higher (Car) |
ANX anxiety disorders, DD dysthymic disorder, MDD major depressive disorder, NC normal controls, PC psychiatric controls, SZ-S schizophrenia spectrum disorders, RMD remitted major depression, PMD persistent major depression, CAR cortisol awakening response
aGroups were further split into: MDD T1 Suicide (attempts prior to T1), MDD T10 Suicide (attempts between T1 and follow up), and MDD No Suicide. MDD T10 showed elevated cortisol levels prior to sleep onset (afternoon, evening, night). MDD T10 also showed elevated cortisol levels 100 min prior and 100 min after sleep onset, but lower levels of cortisol secretion 2-4 h after sleep onset
bYouths with MDD that persisted over 24 months had higher cortisol:DHEA ratios in morning saliva samples than at-risk youths without depression, and at-risk youths who had MDD at 12 months follow-up but remitted by 24 months
cStudy also used CAR (cortisol awakening response) information as predictor of later onset of MDD, and found that individuals who had higher levels of cortisol in their CAR were more likely to become MDD by follow-up. For these purposes, the 56 baseline MDD participants were excluded from that part of the study