Hana Novacenko

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.

Methylphenidate response, psychopathology and tardive dyskinesia as predictors of relapse in schizophrenia

Despite the proven efficacy of acute and maintenance pharmacotherapy in schizophrenia, practical methods for identifying patients who require continuous treatment to prevent relapse have not been established. We hypothesized that a pathologic overactivity of mesolimbic and mesocortical dopamine neural systems, that mediates positive psychotic symptoms in the acute phase of the illness, persists in some outpatients who are vulnerable to relapse despite appearing clinically stable. To test and determine if putative measures of central nervous system dopamine activity predict outcome, 41 stable outpatients receiving neuroleptic maintenance treatment underwent provocative tests with methylphenidate in a randomized double-blind placebo controlled design in which behavioral, neuromotor, biochemical, and cardiovascular responses were measured. Patients were then withdrawn from medication and monitored for 52 weeks, or until relapse. The results indicate that psychotic symptoms and their activation by methylphenidate, and the presence of tardive dyskinesia are associated with each other and with a higher risk of relapse. These findings partially support our hypothesis and offer potentially useful measures for the identification of candidates for reduced dose neuroleptic maintenance treatment strategies in schizophrenia.

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.

The 24-hour pattern of prolactin secretion in depressed and normal adolescents

Plasma prolactin concentrations were measured at 20-min intervals over a 24-hr period in 49 adolescents with major depressive disorder (MDD) and 39 normal control adolescents. Neither the pattern nor the amount of prolactin secretion was significantly different between these two groups. There were significant gender differences, with girls secreting more prolactin than boys, but no significant gender-by-diagnosis interactions were found. With the possible exception of psychosis, dividing the MDD sample based on clinical characteristics failed to reveal differences. These findings are discussed in the context of changes in prolactin in childhood depression using a serotonergic challenge study, as well as in relation to baseline prolactin studies in adult depression.

Hormonal response to fenfluramine challenges in clozapine-treated schizophrenic patients

Clozapine is a dibenzodiazepine derivative with proven antipsychotic efficacy in treatme_nt-refractory schizophrenic patients (Kane et a11988). It is considered an atypical neuroleptic due to its low incidence of extrapyramidal side effects (Kane et a11988), its inability to produce catalepsy (Biirki et al 1975) or block apomorphine-induced stercotypy in animals (Ljungberg and Ungerstedt 1978), and its failure to significantly elevate serum prolactin (Prl) levels (Meltzer et al 1979). Serotonin (5-hydroxytryptamine [5-HT]) agonists are known to stimulate Prl release (Martin and Reichlin 1987). This effect is blocked by 5-HT antagonist agents (Martin and Reichlin 1987). PreclinicaI studies suggest that clozapine is a potent 5-HT antagonist (Fink et al 1984; Lee and Tang 1984). We chose a neuroendocrine strategy to study clozapines effect on the serotonergic system of schizophrenic patients. Fentturamine, a 5-HT agonist, was used as a serotonergic probe. Clozapines ability to inhibit the Prl response to fenfluramine would suggest 5-HT antagonistic properties in humans.

Serial dexamethasone suppression tests in initial suppressors and nonsuppressors treated with electroconvulsive therapy

Four different methods of quantifying the 1-mg Dexamethasone Suppression Test (DST) were contrasted with serial testing in endogenous depressives receiving electroconvulsive therapy (ECT). Of three continuous measures in 38 patients with pretreatment DSTs, only the log-transformed value for plasma cortisol was normally distributed, indicating that it possessed superior psychometric properties. Pretreatment Hamilton Depression Rating Scores (HAM-D) correlated positively with pretreatment DST status, with a similar association noted between posttreatment DST status and HAM-D scores. There was no uniform effect of ECT on the DST. Although pretreatment nonsuppressors showed a trend toward decreased postdexamethasone cortisol values, initial suppressors (cutoff: 5 micrograms/dl) evidenced a significant increase in these values, and 35.3% of initial suppressors were nonsuppressors at final DST assessment. These trends were noted in the DST assessment done following the third ECT treatment, suggesting an effect of regression to the mean. The findings highlight the importance of following initial DST suppressors in studies of this type.

Cortisol and Prolactin Responses to Insulin-induced Hypoglycemia in Prepubertal Major Depressives during Episode and after Recovery

Insulin tolerance tests (ITT) were carried out in 46 drug-free prepubertal children. Thirteen met unmodified Research Diagnostic Criteria (RDC) for major depressive disorder, definite endogenous subtype. Seventeen were classified as nonendogenous major depressive disorder and 16 as nondepressed neurotic disorder (DSM-III). During the depressive episode, depressed children showed no difference from those with neurotic disorders or between depressive subgroups on baseline and ITT-stimulated levels of cortisol or prolactin. On full recovery from depression, ITT-stimulated levels of prolactin and cortisol were unchanged but baseline prolactin and cortisol were elevated in the endogenous subgroup with respect to other groups. These largely negative results contrast with persistently impaired growth hormone responses to the same test reported elsewhere, both during the depressive episode and during recovery.

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.