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Biomedical subjects

M al-Shabbout

Publications and source records attributed to M al-Shabbout.

13 recordsLinked to original sources

Serotonergic functioning in depressed abused children: clinical and familial correlates.

BACKGROUND: The goal of this study was to examine serotonergic functioning and concomitant clinical and familial correlates in depressed abused children. METHODS: L-5-Hydroxytryptophan (L-5-HTP) (0.8 mg/kg) was administered intravenously to 10 depressed abused (MDD-AB), 10 depressed nonabused (MDD-NA), and 10 normal control nonabused (NC-NA) children. The children in the two nonabused cohorts represent a small matched subset of children from a larger interlocking study of the psychobiology of depression. Blood samples for prolactin and cortisol were collected from 30 min before to 2.5 hours after L-5-HTP infusion. RESULTS: The MDD-AB children secreted significantly more prolactin post-L-5-HTP than the children in the other two groups. There were no differences in baseline prolactin or any of the cortisol measures. Total prolactin post-L-5-HTP was significantly correlated with clinical ratings of aggressive behavior (rho = .48). In addition, children with a family history positive for suicide attempt (MDD-AB: n = 7; MDD-NA: n = 5; NC-NA: n = 2) secreted significantly more prolactin post-L-5-HTP than children with no family history of suicide. CONCLUSIONS: Dysregulation in the serotonergic system in abused children appears to be related to both familial and experiential factors.

5-Hydroxytryptophan↗

Neuroendocrine response to 5-hydroxy-L-tryptophan in prepubertal children at high risk of major depressive disorder.

BACKGROUND: Altered serotonergic function has been observed in prepubertal children and adults with an acute episode of major depressive disorder (MDD). However, it is not known whether these alterations are present prior to the onset of MDD. METHODS: A serotonergic precursor, 5-hydroxy-L-tryptophan (L-5HTP) (oxitriptan) (0.8 mg/kg), was administered through an indwelling catheter to 36 children at high risk of MDD (with high family loading for MDD), 31 children with MDD, and 23 low-risk normal controls (with low family loading for mood disorders and no history of psychopathology). Blood samples for cortisol, prolactin (PRL), and growth hormone were obtained every 15 minutes for 180 minutes, beginning 30 minutes before L-5HTP infusion. RESULTS: Children at high risk of MDD and children with MDD had similar hormonal responses following L-5HTP infusion. After controlling for baseline values, both groups secreted significantly less cortisol and more PRL than did the low-risk normal controls, with the PRL finding being limited to girls. There were no between-group differences in baseline cortisol, PRL, or growth hormone secretion measures. CONCLUSIONS: Before the onset of affective illness, high-risk children had the same pattern of neuroendocrine response to the L-5HTP challenge as did children with MDD. These results extend earlier findings of altered serotonergic regulation in association with early-onset depression and indicate that these alterations may represent a trait marker for depression in children.

5-Hydroxytryptophan↗

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.

Adolescent↗

Nocturnal ACTH, cortisol, growth hormone, and prolactin secretion in prepubertal depression.

OBJECTIVE: To examine nocturnal secretion of adrenocorticotropin, cortisol, growth hormone, and prolactin in 38 medically healthy children with prepubertal major depression compared with 28 medically and psychiatrically healthy control children. METHOD: Prior to sampling, subjects underwent an "adaptation night" with the intravenous catheter in place and electroencephalographic (EEG) electrodes for standard all-night polysomnogram. On the following night, plasma samples were obtained every 20 minutes through an indwelling catheter. Hormonal concentrations were measured by specific radioimmunoassay and aligned by EEG-confirmed sleep onset. Areas under the curve were calculated for total secretion and compared using analysis of variance. RESULTS: Prepubertal depressed children had lower cortisol secretion during the first 4 hours after sleep onset compared with controls. Adrenocorticotropin, prolactin, and growth hormone secretion did not differ between groups. Examination of clinical characteristics in depressed children revealed lower nocturnal adrenocorticotropin concentrations in depressed inpatients versus depressed outpatients and in depressed sexually abused versus depressed nonabused children. A significant sex by diagnosis effect revealed lower growth hormone secretion in depressed females compared with depressed males. CONCLUSIONS: In contrast to neuroendocrine challenge studies in these same subjects, nocturnal neuroendocrine measures did not reveal any of the expected group differences. These results emphasize the contrasts between unstimulated and challenge studies of neuroendocrine secretion and of the importance of considering clinical characteristics and maturation influences in biological studies of prepubertal depression.

Adolescent↗

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 adolescent's 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.

Adolescent↗

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.

Aging↗

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.

Adolescent↗

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.

Adolescent↗

Neuroendocrine response to L-5-hydroxytryptophan challenge in prepubertal major depression. Depressed vs normal children.

The neuroendocrine response to L-5-hydroxytryptophan was compared in 37 prepubertal children who met the Research Diagnostic Criteria for major depressive disorder with that in 23 normal children with no lifetime history of any psychiatric disorder and very low rates of depression in both first- and second-degree relatives. Intravenous L-5-hydroxytryptophan (0.8 mg/kg) was given over a 1-hour interval after preloading with oral carbidopa, an inhibitor of peripheral but not central L-5-hydroxytryptophan metabolism. L-5-Hydroxytryptophan, a precursor of serotonin, increases serotonin turnover in the central nervous system when given after carbidopa. Seven (19%) of the 37 children with major depressive disorder and two (9%) of the 23 normal children had nausea or vomiting and therefore did not complete the full infusion. They were subsequently excluded from data analysis. After this stimulation, prolactin, cortisol, and growth hormone secretion were compared between diagnostic groups. The depressed children secreted significantly less cortisol (effect size, 0.70) and significantly more prolactin (effect size, 0.83). There was a sex-by-diagnosis interaction in prolactin response to L-5-hydroxytryptophan and, on examination, the prolactin hypersecretion was seen in depressed girls but not in depressed boys compared with same-sex controls. There was no significant stimulation of growth hormone in either group. These findings are consistent with dysregulation of central serotonergic systems in childhood major depression.

Adult↗

The dexamethasone suppression test in adolescent outpatients with major depressive disorder.

OBJECTIVE: The purpose of the study was to determine whether the dexamethasone suppression test (DST) would discriminate between outpatient adolescents with major depressive disorder and normal adolescent comparison subjects. METHOD: Depressed patients were accepted into the study only if they fulfilled the Research Diagnostic Criteria for major depressive disorder. The depressed subjects (N = 44) and the normal subjects (N = 38) were studied in the same environment and under the same conditions. The subjects received 1 mg of dexamethasone at 11:00 p.m. The next day, blood for determining plasma cortisol concentrations was drawn through an indwelling catheter every 60 minutes from 8:00 a.m. until 11 p.m. RESULTS: After dexamethasone, the cortisol levels of the adolescents with major depressive disorder and the normal subjects were not significantly different. Only six (14%) of the depressed subjects and one (3%) of the normal subjects showed evidence of nonsuppression (cortisol value greater than 5 micrograms/dl). Analyses of subgroups of the depressed patients based on suicidal tendencies and endogenous subtype also failed to reveal significant differences in cortisol values. Estimates of the severity of depression showed significant negative correlations with cortisol values among the depressed patients. CONCLUSIONS: In contrast with previous studies of adolescent inpatients, the DST did not discriminate between the adolescent outpatients with major depressive disorder and the normal comparison subjects in this study. Possible reasons for the discrepancies, such as severity of the depression and inpatient status, are discussed.

Adolescent↗

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).

Adolescent↗

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.

Adolescent↗