Paul Ambrosini

The Psychosocial Functioning and Family Environment of Depressed Adolescents

OBJECTIVE This study examined measures of functional impairment and family relations in a sample of 62 adolescents with major depressive disorder (MDD) and 38 normal controls with no history of psychiatric illness. METHOD Ratings of the following domains were obtained: mother-child relations, father-child relations, spousal relations, sibling relations, peer relations, and school performance. Ratings of each domain for the 3-month period preceding the assessment were derived from information obtained using a semistructured interview administered independently to the adolescents and one of their parents. RESULTS Adolescents with MDD were found to have severe difficulties in all areas. Ninety percent of the depressed adolescents had scores greater than 2 SD above the mean of the normal controls on one or more of the domain ratings. In addition, adolescents with difficulties in parent-child relations were more likely than those adolescents without problems in family relations to have difficulties in peer relations and school performance. CONCLUSIONS The authors discuss the importance of systematically examining psychosocial variables in future studies of the etiology, course, and treatment of MDD in adolescents.

Imipramine in adolescent major depression: plasma level and clinical response

ABSTRACT Thirty‐four adolescents with mean age 14.25 years who met RDC criteria for major depressive disorder as assessed with the K‐SADS, were treated for 6 weeks on a fixed schedule of imipramine hydrochloride titrated to a dosage of 5.0 mg/kg/day except as limited by side effects. Mean dose was 246 mg/day (4.5 mg/kg/day). In spite of good indications of compliance with treatment only 44% of the adolescents improved to the level of no or only slight depressed mood or anhedonia, though most had less depressive symptomatology at the end of treatment. There was neither a linear nor curvilinear relationship between total plasma level of IMI plus DMI and clinical response, despite a wide range of both plasma level (77 ng/ml to 986 ng/ml) and outcome. Adolescents with associated separation anxiety had significantly poorer response to treatment of their depressive disorder than those with major depression alone. Poor response was also weakly associated with being female, having endogenous subtype of depression, and having higher plasma IMI (but not DMI) level. In the context of similar studies of IMI on depression in other age groups, it is hypothesized that high levels of sex hormones during adolescence and young adulthood may interfere with IMIs antidepressant effects. It is concluded that other types of antidepressants should be tested in adolescents with major depression.

Cortisol secretion in adolescents with major depressive disorder

Plasma cortisol concentrations were determined every 20 min for 24 h, in a nonstressful environment, among 48 rigorously assessed, mostly outpatient, drug‐free adolescent subjects during an episode of major depression (MDD) and among 40 normal adolescent subjects. There were no significant differences in the 24‐h mean, peak, or nadir, or the time of the nocturnal rise, in plasma cortisol in the 2 groups. Analyses of different subgroups of MDD adolescents according to suicidality, severity of depression, separation anxiety, psychotic subtype, endogenicity, duration of episode, and sex also revealed no significant group differences. Only one adolescent (with MDD) was identified clearly as a hypersecretor of cortisol. These results indicate that abnormalities of spontaneous cortisol secretion are an unusual finding among adolescents with major depression when studied in a nonstressful environment.

Dexamethasone Suppression Test in Children with Major Depressive Disorder

The authors report a study of 24-hour serial cortisol determinations, measured during baseline and after the administration of 0.25 and 0.5 mg of dexamethasone in a sample of predominantly outpatient children with major depressive disorder, nonaffective psychiatric controls, and normal controls. In this sample, 24-hour baseline cortisol and the dexamethasone suppression test (DST) do not discriminate between the three groups. In addition, the authors measured 24-hour serum dexamethasone levels. There were no significant between group differences in serum dexamethasone. These results raise questions as to the utility of this test in the diagnosis of affective disorders in children. Possible reasons for the discrepancies in the dexamethasone suppression test results between in- and outpatient studies are discussed.

Growth hormone response to desmethylimipramine in depressed and suicidal adolescents

Desipramine 75 mg i.m. was given in the morning to 20 adolescents with major depressive disorder and 23 normal controls. Depressed adolescents secreted significantly less growth hormone (GH) over the next 2 h than did normal adolescents, although a substantial proportion of the differences were accounted for by the depressed adolescents who had a specific suicidal plan or attempt during the episode. Severity of depression or the presence of other depressive symptoms did not predict GH secretion within the depressed group. Age, sex and maturational factors in the control of GH are discussed. It is concluded that these differences in GH secretion probably reflect differences in CNS beta-adrenergic and/or serotonergic function. Suicidality and depression may have different psychobiological correlates in adolescents.

Regulation of Sleep and Growth Hormone in Adolescent Depression

This article reviews findings of sleep, growth hormone (GH), and cortisol measures from a number of separate controlled studies of prepubertal and adolescent depression carried out by Puig-Antich and colleagues since 1978. New data are presented comparing 24-hour GH measures in adolescents with major depressive disorder (MDD) (N = 44; mean age = 14.8 +/- 2.0) to normal control adolescents (N = 37; mean age = 15.3 +/- 1.5). There were no significant overall group differences in summary GH measures between MDD and normal controls. Splitting the MDD group on the basis of suicidality (definite plan or attempt) (N = 20), revealed a significant blunting of sleep GH compared to the nonsuicidal group (N = 24). These results are discussed in the context of the other sleep and neuroendocrine findings in this population, with evidence for dysregulation around sleep onset. The influences of development on sleep and GH regulation are also considered.

Relative Safety of Single Versus Divided Dose Imipramine in Adolescent Major Depression

Abstract Twenty-nine adolescents with Major Depressive Disorder were treated with imipramine on a t.i.d. dosage schedule for 3 weeks titrating to a maximal 5.0 mg/kg/day as limited by side effects (X = 4.5 ± 0.7). They were then randomly divided into two groups: 16 received their total dose at 10 P.M., after standard divided doses at 7 A.M. and 3 P.M. that same day, and then no more imipramine during the subsequent 24 hours, whereas 13 continued t.i.d. dosage. EKG and plasma TCA levels in both groups were serially examined over the next 24 hours. There were no significant differences between groups in the per subject means or maxima of any EKG parameter. These data suggest that a once daily dosage schedule for imipramine is safe in adolescents once they are at steady rate. Although there was a strong relationship between the tricyclic plasma levels and EKG parameters throughout the day, EKG parameters cannot be used to predict plasma levels—there was wide variation in this relationship between individuals, and even within individual adolescents the plasma level could change over a wide range without any change in EKG parameters.

Hormonal Responses to Dextroamphetamine in Depressed and Normal Adolescents

Because of its neuroendocrine effects, amphetamine infusion has been used as a probe to investigate neurobiological correlates of depressive illness. In two separate studies, a total of 72 adolescents with major depressive disorder and 66 normal adolescents were given dextroamphetamine, 0.15 mg/kg, intravenously. Their cortisol, growth hormone, and prolactin responses were measured. These endocrine responses did not reliably distinguish adolescents with major depressive disorder from those without it, nor did they reliably delineate any specific depressive subgroup. These findings are compared with those from similar studies of adult depression.

Preliminary Report: Amantadine Hydrochloride in Childhood Enuresis

This pilot study tests the hypotheses that a do-pamine agonist would be beneficial in childhood enuresis. Amantadine hydrochloride, a dopamine agonist and antiviral agent, was administered openly for a 4-week period to six primary enuretic children (five boys and one girl) with a mean age of 9:1. The mean baseline wetting frequency was 0.739 (range, 0.429 to 0.909). During amantadine treatment, average wetting frequency decreased to 0.436 (range, 0.210 to 0.690). This 41% reduction was significant at the p < 0.05 level (Wilcoxon). Response persisted during a 2-week follow-up period off medication as the average wetting frequency (0.381) remained significantly less than baseline. There was no significant difference between the 4-week drug trial and follow-up values. These preliminary findings support the hypothesis that dopamine agonists influence urinary continence in enuretic children. Further investigations are warranted to expand this preliminary data and clarify the physiological and biochemical aspects of this disorder.