Mayadah Al-Shabbout

24-hour cortisol measures in adolescents with major depression : a controlled study

Plasma cortisol levels were determined every 20 min for 24 hr in depressed adolescents (n = 27) meeting research diagnostic criteria (RDC) for major depressive disorder (MDD) and normal controls (n = 32). All subjects were between 12 and 18 years of age, at least Tanner Stage III of sexual development, medically healthy, and medication free at the time of the studies. The results showed that cortisol secretory patterns were very similar between the two groups with the exception that the depressed adolescents showed significantly elevated cortisol levels around sleep onset (a period when cortisol is usually suppressed). Subgroup analyses showed that most of these differences were contributed by the suicidal/inpatient depressed adolescents. The cause of the elevated cortisol during the normally quiescent period warrants further investigation and may be related to other biological disturbances around sleep onset (difficulty initiating sleep, reduced rapid eye movement (REM) latency, and alterations in sleep-stimulated growth hormone secretion).

Stressful life events in depressed adolescents: the role of dependent events during the depressive episode.

OBJECTIVE To examine the relationship between stressful life events and major depressive disorder (MDD) in adolescents. METHOD Adolescents (aged 12 to 18 years) with a current episode of MDD based on Research Diagnostic Criteria (n = 39) and normal controls free of any Axis I lifetime psychiatric disorder (n = 35) were assessed using the Life Events Record. RESULTS MDD and normal control adolescents had similar rates of total stressful life events in the year before being interviewed. Stressful life events were dichotomized into those that were most likely either independent of or dependent on the adolescents influence/behavior. Depressed adolescents had significantly more dependent stressful life events during the previous year than did the normal controls. Further analyses showed that depressed adolescents with dependent stressful life events scored lower on symptom clusters and accordingly were less severely depressed than depressed adolescents without dependent life events. CONCLUSIONS The results of this study indicate that depressed adolescents have an increased risk for experiencing dependent life events. Furthermore, these data suggest that dependent life events in depressed adolescents are differentially associated with the type and severity of symptom presentation. The temporal occurrence, severity, and type of stressful life events as they relate to the onset, phenotypic expression, and maintenance of depression in adolescents need to be more fully understood.

Sleep onset abnormalities in depressed adolescents

Sleep measures were obtained in 16 depressed and 21 control adolescents following 1 week of adherence to a uniformly imposed and strictly enforced sleep/wake schedule. Three nights of baseline electroencephalographic (EEG) sleep on the same 10:00 PM to 7:00 AM schedule revealed prolonged sleep latency and reduced rapid eye movement (REM) latency in the depressed adolescents. Following baseline measures, sleep was restricted for 2 nights (10:00 PM-4:00 AM) and measures of recovery sleep were obtained showing further sleep latency differences. There was no evidence for delta sleep changes or sleep continuity differences in depressed adolescents. These results suggest that control over sleep/wake schedules is an important methodological issue in adolescent sleep studies. Furthermore, the findings are consistent with a larger body of evidence indicating that dysregulation near sleep onset represents a primary psychobiological change in early-onset depression.

Electroencephalographic sleep measures in prepubertal depression

Two nights of electroencephalographic (EEG) sleep recording were performed in a group of prepubertal subjects with major depressive disorder (MDD) (n = 36, mean age = 10.4, SD = 1.5) and age-matched normal control children (n = 18, mean age = 10.1, SD = 1.6). All subjects were medically healthy and free of medications at the time of the study. There were no significant group differences for any major sleep variable after the initial adaptation night in this study. One subgroup of MDD subjects (n = 8) showed reduced REM latency on both recording nights, decreased stage 4 sleep, and increased REM time; this subgroup had significantly higher severity scores for depression but did not otherwise appear to be clinically distinct from the rest of the MDD subjects. Overall, the results indicate that the EEG sleep changes associated with depression in adults occurred less frequently in prepubertal MDD subjects.

The Dexamethasone Suppression Test in children and adolescents: A review and a controlled study

Dexamethasone Suppression Test (DST) studies conducted in children and adolescents are reviewed, together with factors hypothesized to explain discrepancies in rates of DST nonsuppression across studies. These factors are then examined in a controlled study of 27 adolescents with major depressive disorder (MDD) and 34 normal controls (NC). Subjects were given 1 mg of dexamethasone at 11:00 PM, and the following day serum samples for cortisol were collected each hr from 8 AM to 11 PM through an indwelling catheter. There were no significant differences found between the MDD and NC subjects on any postdexamethasone cortisol measure. Further, cortisol suppressors and nonsuppressors were not distinguished by any of the hypothesized factors identified from the review, including inpatient status, presence of suicidality, endogenous features, psychotic symptoms, or prior history of MDD. Questions about the appropriateness of the 1 mg dose of dexamethasone (currently the standard dose used with adolescents) are raised, together with a discussion of the effects of stress on DST findings.

Cellular Immunity in Depressed, Conduct Disorder, and Normal Adolescents: Role of Adverse Life Events

OBJECTIVE To determine whether adolescents with major depressive disorder have disturbances in their cellular immunity and to study whether the immunological changes detected are specific to depression or are general responses to stress. METHOD Twenty subjects with major depressive disorder, 17 nondepressed subjects with conduct disorder, and 17 normal adolescents were recruited. Subjects were assessed with a clinical interview for DSM-III-R and a modified version of the Coddington Life Events Checklist. Blood samples were drawn for total white blood cells, lymphocytes subsets, natural killer cell activity, lymphocyte proliferation response to phytohemagglutinin, and cortisol plasma levels. RESULTS Overall, there were no significant between-group differences in any of the cellular immune measurements. Natural killer cell activity was significantly negatively correlated with past year and lifetime adverse life events across all effector-target cell ratios. Controlling for diagnoses and socioeconomic status yielded similar results. There were no significant effects of age, sex, race, sleep, nutrition, cigarette use, menstrual cycle, or cortisol on any of the immunological variables. CONCLUSIONS In this sample of adolescents, we found that independent of the diagnoses and socioeconomic status, increases in adverse life events were associated with low natural killer cell activity.

Cholinergic REM induction test with arecoline in depressed children

Children with major depressive disorder often fail to exhibit electroencephalographic (EEG) sleep abnormalities similar to those reported in depressed adults. It was hypothesized that a cholinergic rapid eye movement (REM) induction test would contribute to the identification of EEG sleep abnormalities in depressed children. To test this hypothesis, prepubertal children meeting research diagnostic criteria for major depressive disorder (n = 33) and carefully screened healthy control children (n = 15) were enrolled in a 4-day psychobiologic protocol that included 1 night with infusion of arecoline (0.5 mg) during the first non-REM sleep period. Although there had been no significant group differences in baseline sleep measures, results on the arecoline night revealed significantly shorter REM latency in the group of depressed children compared with the control children (mean +/- SD = 105 +/- 51 minutes vs. 140 +/- 46 minutes). The design of the protocol (with an interval break immediately preceding the arecoline night) prevented a direct estimation of arecoline effects within subjects; however, these data provide promising preliminary results regarding cholinergic REM induction tests in childhood depression.

Stressful life events influence nocturnal growth hormone secretion in depressed children

Pharmacologic challenge studies of growth hormone (GH) secretion in depressed children, adolescents, and adults have consistently reported blunted GH responses (Ansseau et al 1984; Jarrett et al 1990; Puig-Antich et al 1984a; Ryan et al 1988, 1994). In contrast, studies of baseline nocturnal (or sleep stimulated) GH have revealed varied results across age groups. Studies of depressed adults have found blunted nocturnal GH secretion in recurrent depressives (Jarrett et al 1990; Steiger et al 1989; Voderholzer et al 1993), which remains blunted over time (Jarrett et al 1994) and predicts recurrence (Franz et al 1995); however, the findings from nocturnal GH studies in depressed children and adolescents have been inconsistent. In an early report, Puig-Antich et al (1984b) found that depressed children hypersecreted GH during sleep compared to controls. In contrast, a larger study of prepubertal depressed children found no differences in nocturnal GH secretion compared to normal controls (DeBellis et al 1995). One study of depressed adolescents found nocturnal GH to be elevated (Kutcher et al 1988). Another study of adolescents found no differences in GH secretion between depressed and normal controls during the night (Dahl et al 1992), but a subgroup of suicidal depressed adolescents did show blunted nocturnal GH (Dahl et al 1992). Since age has been shown to effect GH secretion beginning in early adolescence (Copinschi and Van Canter 1995), it is possible that maturational changes in GH regulation associated