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Context: Individuals with early onset of bipolar disorder are at high risk for suicide. Yet, no study to date has examined factors associated with prospective risk for suicide attempts among youth with bipolar disorder., Objective: To examine past, intake, and follow-up predictors of prospectively observed suicide attempts among youth with bipolar disorder., Design: We interviewed subjects, on average, every 9 months over a mean of 5 years using the Longitudinal Interval Follow-up Evaluation., Setting: Outpatient and inpatient units at 3 university centers., Participants: A total of 413 youths (mean [SD] age, 12.6 [3.3] years) who received a diagnosis of bipolar I disorder (n=244), bipolar II disorder (n=28), or bipolar disorder not otherwise specified (n=141)., Main Outcome Measures: Suicide attempt over prospective follow-up and past, intake, and follow-up predictors of suicide attempts., Results: Of the 413 youths with bipolar disorder, 76 (18%) made at least 1 suicide attempt within 5 years of study intake; of these, 31 (8% of the entire sample and 41% of attempters) made multiple attempts. Girls had higher rates of attempts than did boys, but rates were similar for bipolar subtypes. The most potent past and intake predictors of prospectively examined suicide attempts included severity of depressive episode at study intake and family history of depression. Follow-up data were aggregated over 8-week intervals; greater number of weeks spent with threshold depression, substance use disorder, and mixed mood symptoms and greater number of weeks spent receiving outpatient psychosocial services in the preceding 8-week period predicted greater likelihood of a suicide attempt., Conclusions: Early-onset bipolar disorder is associated with high rates of suicide attempts. Factors such as intake depressive severity and family history of depression should be considered in the assessment of suicide risk among youth with bipolar disorder. Persistent depression, mixed presentations, and active substance use disorder signal imminent risk for suicidal behavior in this population.

Context: There was a paucity of comparative pharmacological research for initial treatment of bipolar I disorder, manic or mixed phase, in children and adolescents., Objective: To investigate which medication to administer first to antimanic medication-naive subjects., Design, Setting, and Participants: The Treatment of Early Age Mania (TEAM) study recruited 6- to 15-year-old children and adolescents with DSM-IV bipolar I disorder (manic or mixed phase) at 5 US sites from 2003 to 2008 into a controlled, randomized, no-patient-choice, 8-week protocol. Blinded, independent evaluators conducted all baseline and end-point assessments., Interventions: Subjects received a titrated schedule of lithium, divalproex sodium, or risperidone. Medications were increased weekly only if there was inadequate response, and no dose-limiting adverse effects, to maximum doses of lithium carbonate (1.1-1.3 mEq/L), divalproex sodium (111-125 μg/mL), and risperidone (4-6 mg)., Main Outcome Measures: Primary outcome measures were the Clinical Global Impressions for Bipolar Illness Improvement-Mania and the Modified Side Effects Form for Children and Adolescents., Results: There were 279 antimanic medication-naive subjects (mean [SD] age, 10.1 [2.8] years; 50.2% female) who had the following characteristics: 100% elated mood and/or grandiosity, 77.1% psychosis, 97.5% mixed mania, 99.3% daily rapid cycling, and mean (SD) mania duration of 4.9 (2.5) years. The mean (SD) titrated lithium level was 1.09 (0.34) mEq/L, and the mean (SD) divalproex sodium level was 113.6 (23.0) μg/mL. The mean (SD) titrated risperidone dose was 2.57 (1.21) mg. Higher response rates occurred with risperidone vs lithium (68.5% vs 35.6%; χ(2)(1) = 16.9, P < .001) and vs divalproex sodium (68.5% vs 24.0%; χ(2)(1) = 28.3, P < .001). Response to lithium vs divalproex sodium did not differ. The discontinuation rate was higher for lithium than for risperidone (χ(2)(1) = 6.4, P = .011). Increased weight gain, body mass index, and prolactin level occurred with risperidone vs lithium (F(1,212) = 45.5, P < .001; F(1,212) = 39.1, P < .001; and F(1,213) = 191.4, P < .001, respectively) and vs divalproex sodium (F(1,212) = 34.7, P < .001; F(1,212) = 45.3, P < .001; and F(1,213) = 209.4, P < .001, respectively). The thyrotropin level increased in subjects taking lithium (t(62) = 11.3, P < .001)., Conclusions: Risperidone was more efficacious than lithium or divalproex sodium for the initial treatment of childhood mania but had potentially serious metabolic effects., Trial Registration: clinicaltrials.gov Identifier: NCT00057681

Context: Many youth with depression do not respond to initial treatment with selective serotonin reuptake inhibitors (SSRIs), and this is associated with higher costs. More effective treatment for these youth may be cost-effective., Objective: To evaluate the incremental cost-effectiveness over 24 weeks of combined cognitive behavior therapy plus switch to a different antidepressant medication vs medication switch only in adolescents who continued to have depression despite adequate initial treatment with an SSRI., Design: Randomized controlled trial., Setting: Six US academic and community clinics., Patients: Three hundred thirty-four patients aged 12 to 18 years with SSRI-resistant depression., Intervention: Participants were randomly assigned to (1) switch to a different medication only or (2) switch to a different medication plus cognitive behavior therapy., Main Outcome Measures: Clinical outcomes were depression-free days (DFDs), depression-improvement days (DIDs), and quality-adjusted life-years based on DFDs (DFD-QALYs). Costs of intervention, nonprotocol services, and families were included., Results: Combined treatment achieved 8.3 additional DFDs (P = .03), 0.020 more DFD-QALYs (P = .03), and 11.0 more DIDs (P = .04). Combined therapy cost $1633 more (P = .01). Cost per DFD was $188 (incremental cost-effectiveness ratio [ICER] = $188; 95% confidence interval [CI], -$22 to $1613), $142 per DID (ICER = $142; 95% CI, -$14 to $2529), and $78,948 per DFD-QALY (ICER = $78,948; 95% CI, -$9261 to $677,448). Cost-effectiveness acceptability curve analyses suggest a 61% probability that combined treatment is more cost-effective at a willingness to pay $100,000 per QALY. Combined treatment had a higher net benefit for subgroups of youth without a history of abuse, with lower levels of hopelessness, and with comorbid conditions., Conclusions: For youth with SSRI-resistant depression, combined treatment decreases the number of days with depression and is more costly. Depending on a decision maker's willingness to pay, combined therapy may be cost-effective, particularly for some subgroups., Trial Registration: clinicaltrials.gov Identifier: NCT00018902.

Context: Whether offspring of parents with bipolar disorder (BP) are at specifically high risk to develop BP and other psychiatric disorders has not been adequately studied., Objective: To evaluate lifetime prevalence and specificity of psychiatric disorders in offspring of parents with BP-I and BP-II., Design: Offspring aged 6 to 18 years who have parents with BP and community control subjects were interviewed with standardized instruments. All research staff except the statistician were blind to parental diagnoses., Setting: Parents with BP were recruited primarily through advertisement and outpatient clinics. Control parents were ascertained by random-digit dialing and were group matched for age, sex, and neighborhood to parents with BP., Participants: Three hundred eighty-eight offspring of 233 parents with BP and 251 offspring of 143 demographically matched control parents., Main Outcome Measures: Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) Axis I disorders., Results: Adjusting for demographic factors, living with 1 vs both biological parents, both biological parents' non-BP psychopathology, and within-family correlations, offspring of parents with BP showed high risk for BP spectrum disorders (odds ratio [OR] = 13.4; 95% confidence interval [CI], 2.9-61.6) and any mood (OR = 5.2; 95% CI, 2.3-11.4), anxiety (OR = 2.3; 95% CI, 1.3-4.0), and Axis I (OR = 2.2; 95% CI, 1.5-3.3) disorders. Offspring of parents with BP with high socioeconomic status showed more disruptive behavior disorders and any Axis I disorders than offspring of control parents with high socioeconomic status. Families in which both parents had BP had more offspring with BP than families with only 1 parent with BP (OR = 3.6; 95% CI, 1.1-12.2). More than 75.0% of offspring who developed BP had their first mood episode before age 12 years, with most of these episodes meeting criteria for BP not otherwise specified and, to a lesser degree, major depression., Conclusions: Offspring of parents with BP are at high risk for psychiatric disorders and specifically for early-onset BP spectrum disorders. These findings further support the familiality and validity of BP in youth and indicate a need for early identification and treatment.

Context: Family interventions have been found to hasten episode recovery and delay recurrences among adults with bipolar disorder., Objective: To examine the benefits of family-focused treatment for adolescents (FFT-A) and pharmacotherapy in the 2-year course of adolescent bipolar disorder., Design: Two-site outpatient randomized controlled trial with 2-year follow-up., Patients: A referred sample of 58 adolescents (mean [SD] age, 14.5 [1.6] years) with bipolar I (n = 38), II (n = 6), or not otherwise specified disorder (n = 14) with a mood episode in the prior 3 months., Interventions: Patients were randomly assigned to FFT-A and protocol pharmacotherapy (n = 30) or enhanced care (EC) and protocol pharmacotherapy (n = 28). The FFT-A consisted of 21 sessions in 9 months of psychoeducation, communication training, and problem-solving skills training. The EC consisted of 3 family sessions focused on relapse prevention., Main Outcome Measures: Independent "blind" evaluators assessed patients every 3 to 6 months for 2 years. Outcomes included time to recovery from the index episode, time to recurrence, weeks in episode or remission, and mood symptom severity scores., Results: Analyses were by intent to treat. Rates of 2-year study completion did not differ across the FFT-A (60.0%) and EC conditions (64.3%). Although there were no group differences in rates of recovery from the index episode, patients in FFT-A recovered from their baseline depressive symptoms faster than patients in EC (hazard ratio, 1.85; 95% confidence interval, 1.04-3.29; P = .04). The groups did not differ in time to recurrence of depression or mania, but patients in FFT-A spent fewer weeks in depressive episodes and had a more favorable trajectory of depression symptoms for 2 years., Conclusions: Family-focused therapy is effective in combination with pharmacotherapy in stabilizing bipolar depressive symptoms among adolescents. To establish full recovery, FFT-A may need to be supplemented with systematic care interventions effective for mania symptoms.

Context: Children and adolescents who present with manic symptoms frequently do not meet the full DSM-IV criteria for bipolar I disorder (BP-I)., Objective: To assess the clinical presentation and family history of children and adolescents with BP-I, bipolar II disorder (BP-II), and bipolar disorder not otherwise specified (BP-NOS)., Design: Subjects and their primary caretaker were assessed by semistructured interview, and family psychiatric history was obtained from interview of the primary caretaker., Setting: Outpatient and inpatient units at 3 university centers., Participants: A total of 438 children and adolescents (mean +/- SD age, 12.7 +/- 3.2 years) with BP-I (n = 255), BP-II (n = 30), or BP-NOS (n = 153)., Main Outcome Measures: Lifetime psychiatric history and family history of psychiatric disorders., Results: Youth with BP-NOS were not diagnosed as having BP-I primarily because they did not meet the DSM-IV duration criteria for a manic or mixed episode. There were no significant differences among the BP-I and BP-NOS groups in age of onset, duration of illness, lifetime rates of comorbid diagnoses, suicidal ideation and major depression, family history, and the types of manic symptoms that were present during the most serious lifetime episode. Compared with youth with BP-NOS, subjects with BP-I had more severe manic symptoms, greater overall functional impairment, and higher rates of hospitalization, psychosis, and suicide attempts. Elevated mood was present in 81.9% of subjects with BP-NOS and 91.8% of subjects with BP-I. Subjects with BP-II had higher rates of comorbid anxiety disorders compared with the other 2 groups and had less functional impairment and lower rates of psychiatric hospitalization than the subjects with BP-I., Conclusions: Children and adolescents with BP-II and BP-NOS have a phenotype that is on a continuum with that of youth with BP-I. Elevated mood is a common feature of youth with BP-spectrum illness.

Context: Despite the high morbidity associated with bipolar disorder (BP), few studies have prospectively studied the course of this illness in youth., Objective: To assess the longitudinal course of BP spectrum disorders (BP-I, BP-II, and not otherwise specified [BP-NOS]) in children and adolescents., Design: Subjects were interviewed, on average, every 9 months for an average of 2 years using the Longitudinal Interval Follow-up Evaluation., Setting: Outpatient and inpatient units at 3 university centers., Participants: Two hundred sixty-three children and adolescents (mean age, 13 years) with BP-I (n = 152), BP-II (n = 19), and BP-NOS (n = 92)., Main Outcome Measures: Rates of recovery and recurrence, weeks with syndromal or subsyndromal mood symptoms, changes in symptoms and polarity, and predictors of outcome., Results: Approximately 70% of subjects with BP recovered from their index episode, and 50% had at least 1 syndromal recurrence, particularly depressive episodes. Analyses of weekly mood symptoms showed that 60% of the follow-up time, subjects had syndromal or subsyndromal symptoms with numerous changes in symptoms and shifts of polarity, and 3% of the time, psychosis. Twenty percent of BP-II subjects converted to BP-I, and 25% of BP-NOS subjects converted to BP-I or BP-II. Early-onset BP, BP-NOS, long duration of mood symptoms, low socioeconomic status, and psychosis were associated with poorer outcomes and rapid mood changes. Secondary analyses comparing BP-I youths with BP-I adults showed that youths significantly more time symptomatic and had more mixed/cycling episodes, mood symptom changes, and polarity switches., Conclusions: Youths with BP spectrum disorders showed a continuum of BP symptom severity from subsyndromal to full syndromal with frequent mood fluctuations. Results of this study provide preliminary validation for BP-NOS.

Background: Although adoption, twin, and family studies have shown that suicidal behavior is familial, the risk factors for familial transmission from parent to child remain unclear., Methods: A high-risk family study was conducted comparing the offspring of 2 mood-disordered groups: suicide attempters and nonattempters. Recruited from 2 sites, probands were 81 attempters and 55 nonattempters, with 183 and 116 offspring, respectively. Offspring were assessed by investigators masked to proband status. Probands and offspring were assessed with respect to psychopathologic findings, suicide attempt history, impulsive aggression, and exposure to familial environmental stressors., Results: Offspring of attempters had a 6-fold increased risk of suicide attempts relative to offspring of nonattempters. Familial transmission of suicide attempt was more likely if (1) probands had a history of sexual abuse and (2) offspring were female and had a mood disorder, substance abuse disorder, increased impulsive aggression, and a history of sexual abuse., Conclusions: The offspring of mood-disordered suicide attempters are at markedly increased risk for suicide attempts themselves. Familial transmission of suicidal behavior in families with mood disorders almost always requires transmission of a mood disorder and is also related to the offspring's impulsive aggression and the familial transmission of sexual abuse. Early treatment of mood disorders and targeting impulsive aggression and sexual trauma may be helpful in the prevention and treatment of suicidal behavior in families with mood disorders.

Background: Alterations in amygdala function have been implicated in the pathophysiological characteristics of adult anxiety and depressive disorders. Studies with healthy adults and children, as well as with adults who have amygdala lesions, have found facial expressions of emotion to be useful probes of amygdala activity. Our study examined the amygdala response to fearful and neutral facial expressions in healthy, anxious, and depressed children. We hypothesized that children with anxiety and depression may show atypical amygdala responses to emotional stimuli., Methods: Twelve children (8-16 years of age) with generalized anxiety or panic disorder and 12 healthy comparison children underwent noninvasive functional magnetic resonance imaging while viewing photographs of fearful and neutral facial expressions. In a second comparison, 5 girls with major depressive disorder were compared with 5 anxious and 5 healthy girls from the previous sample., Results: Children with anxiety disorders showed an exaggerated amygdala response to fearful faces compared with healthy children, whereas depressed children showed a blunted amygdala response to these faces. In addition, the magnitude of the amygdala's signal change between fearful and neutral faces was positively correlated with the severity of everyday anxiety symptoms., Conclusions: Our results suggest that amygdala function is affected in both anxiety and depression during childhood and adolescence. Moreover, this disruption appears to be specific to the child's own rating of everyday anxiety.

Background: Decreased growth hormone (GH) response to pharmacologic stimulation has been found in children and adolescents during an episode of major depressive disorder and after recovery. In this study, we sought to determine whether GH secretion is similarly altered in children and adolescents who had never experienced depression but were at high risk of developing depression., Methods: Subjects were 8 through 16 years of age and selected for high- and low-risk status according to familial loading for mood disorders. Sixty-four high-risk and 55 low-risk healthy subjects participated in the study, which assessed the following GH measures: (1) GH before growth hormone-releasing hormone (GHRH) infusion, every 15 minutes for 30 minutes; (2) GH response after intravenous infusion of GHRH (0.1 microg/kg), every 15 minutes for 90 minutes; and (3) nocturnal GH every 20 minutes from 9 PM until morning awakening., Results: After stimulation with GHRH, the high-risk subjects secreted significantly less GH compared with the low-risk healthy controls (effect sizes for mean and peak GH, 0.52 [P =.007] and 0.40 [P =.04], respectively). In contrast, there were no between-group differences in the pre-GHRH and nocturnal GH secretion levels. Exposure to recent stressors was not associated with GH secretion., Conclusions: Taken together with previous evidence of decreased GH after GHRH infusion in acutely depressed and recovered children, these results indicate that the decreased GH response found in high-risk subjects may represent a trait marker for depression in children and adolescents.

Background: Cognitive behavioral therapy has been shown to be more efficacious than alternative psychosocial interventions for the acute treatment of adolescents with major depressive disorder. However, the long-term impact of brief psychosocial interventions on the course of adolescent depression is not well established., Methods: One hundred seven adolescents with major depressive disorder randomly assigned to 12 to 16 weeks of cognitive behavioral therapy, systemic behavioral family therapy, or nondirective supportive therapy were evaluated for 2 years after the psychotherapy trial to document the subsequent course and predictors of major depressive disorder., Results: There were no long-term differential effects of the 3 psychotherapies. Most participants (80%) recovered (median time, 8.2 months from baseline), and 30% had a recurrence (median time, 4.2 months from recovery). Twenty-one percent were depressed during at least 80% of the follow-up period. Severity of depression (at baseline) and presence of self-reported parent-child conflict (at baseline and during the follow-up period) predicted lack of recovery, chronicity, and recurrence. Despite the similarity to clinically referred patients at baseline, patients recruited via advertisement were less likely to experience a recurrence., Conclusions: There were no significant differences in long-term outcome among cognitive behavioral therapy, systematic behavioral family therapy, and nondirective supportive therapy. While most participants in this study eventually recovered, those with severe depression and self-perceived parent-child conflict are at greater risk for chronic depression and recurrences.

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.

Background: Disturbances in the orbital prefrontal cortex and its ventral striatal target fields have been identified in neuroimaging studies of obsessive-compulsive disorder (OCD). In animal models and studies of patients with lesions to this brain circuitry, a selective disturbance in the ability to suppress responses to irrelevant stimuli has been demonstrated. Such a deficit in response suppression might underlie the apparent inhibitory deficit suggested by the symptoms of OCD. To date, little direct evidence of such a deficit has been reported. Further, although OCD commonly emerges during childhood or adolescence, few studies have examined psychotropic-naive pediatric patients near the onset of illness to find the possible role of atypical developmental processes in this disorder., Methods: Oculomotor tests were administered to 18 psychotropic medication-naive, nondepressed patients with OCD aged 8.8 to 16.9 years and 18 case-matched healthy comparison subjects to assess the following 3 well-delineated aspects of prefrontal cortical function: the ability to suppress responses, the volitional execution of delayed responses, and the anticipation of predictable events., Results: A significantly higher percentage of response suppression failures was observed in patients with OCD (P = .003), particularly in younger patients compared with their case-matched controls. No significant differences between patients with OCD and controls were observed on other prefrontal cortical functions. Severity of OCD symptoms was related to response suppression deficits., Conclusions: A basic disturbance of behavioral inhibition in OCD was detected that may underlie the repetitive symptomatic behavior that characterizes the illness.

Background: Abnormalities in frontostriatal circuits have been implicated in obsessive-compulsive disorder (OCD). Although OCD commonly emerges during childhood or adolescence, few studies have examined frontostriatal anatomy in psychotropic-naive children with OCD near the onset of illness to determine the possible role of atypical developmental processes in this disorder., Methods: Magnetic resonance imaging scans from 19 children with OCD who had not been exposed to psychotropic drugs, aged 7 to 18 years, and 19 case-matched healthy control subjects were analyzed to determine the volumes of the following structures: prefrontal cortex, striatum (caudate and putamen), lateral and third ventricles, and intracranial volume., Results: Patients with OCD had significantly smaller striatal volumes and significantly larger third ventricle volumes than controls, but did not differ in prefrontal cortical, lateral ventricular, or intracranial volumes. Striatal volumes were inversely correlated with OCD symptom severity but not illness duration., Conclusions: Our findings provide new evidence of abnormalities of the striatum in pediatric OCD. These results are preliminary, given the small sample size.

Background: Previous studies in nonclinical samples have shown psychosocial treatments to be efficacious in the treatment of adolescent depression, but few psychotherapy treatment studies have been conducted in clinically referred, depressed adolescents., Methods: One hundred seven adolescent patients with DSM-III-R major depressive disorder (MDD) were randomly assigned to 1 of 3 treatments: individual cognitive behavior therapy, systemic behavior family therapy (SBFT), or individual nondirective supportive therapy (NST). Treatments were 12 to 16 sessions provided in as many weeks. Intent-to-treat analyses were conducted using all follow-up data., Results: Of the 107 patients enrolled in the study, 78 (72.9%) completed the study, 4 (3.7%) never initiated treatment, 10 (9.3%) had exclusionary criteria that were undetected at entry, 8 (7.5%) dropped out, and 7 (6.5%) were removed for clinical reasons. Cognitive behavior therapy showed a lower rate of MDD at the end of treatment compared with NST (17.1% vs 42.4%; P = .02), and resulted in a higher rate of remission (64.7%, defined as absence of MDD and at least 3 consecutive Beck Depression Inventory scores < 9) than SBFT (37.9%; P = .03) or NST (39.4%; p = .04). Cognitive behavior therapy resulted in more rapid relief in interviewer-rated (vs both treatments, P = .03) and self-reported depression (vs SBFT, P = .02). All 3 treatments showed significant and similar reductions in suicidality and functional impairment. Parents' views of the credibility of cognitive behavior therapy improved compared with parents' views of both SBFT (P = .01) and NST (P = .05)., Conclusions: Cognitive behavior therapy is more efficacious than SBFT or NST for adolescent MDD in clinical settings, resulting in more rapid and complete treatment response.

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.