0
We're unable to sign you in at this time. Please try again in a few minutes.
Retry
We were able to sign you in, but your subscription(s) could not be found. Please try again in a few minutes.
Retry
There may be a problem with your account. Please contact the AMA Service Center to resolve this issue.
Contact the AMA Service Center:
Telephone: 1 (800) 262-2350 or 1 (312) 670-7827  *   Email: subscriptions@jamanetwork.com
Error Message ......
Original Article |

Growth Hormone Secretion in Children and Adolescents at High Risk for Major Depressive Disorder FREE

Boris Birmaher, MD; Ronald E. Dahl, MD; Douglas E. Williamson, PhD; James M. Perel, PhD; David A. Brent, MD; David A. Axelson, MD; Joan Kaufman, PhD; Lorah D. Dorn, PhD; Stacy Stull, MS; Uma Rao, MD; Neal D. Ryan, MD
[+] Author Affiliations

From the Department of Psychiatry, University of Pittsburgh School of Medicine, Western Psychiatric Institute and Clinic, Pittsburgh, Pa.


Arch Gen Psychiatry. 2000;57(9):867-872. doi:10.1001/archpsyc.57.9.867.
Text Size: A A A
Published online

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 µg/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.

Figures in this Article

DECREASED GROWTH hormone (GH) secretion in response to pharmacologic stimulation with various substances has been reported in children and adolescents with major depressive disorder (MDD).1,2 Similarly, decreased GH secretion after stimulation has been reported in most studies of adults with MDD.3,4 Overall, the results of these studies are consistent in suggesting that GH secretion is decreased after pharmacologic stimulation among depressed subjects across the age span. In contrast, studies1,39 evaluating the 24-hour baseline or nocturnal secretion of GH in acutely depressed children, adolescents, and adults have yielded inconsistent results.

Since these pharmacologic stimulation studies were conducted while the subjects were depressed, it is unclear whether the decreased GH response is a function of the depressive condition or also can be found in susceptible individuals prior to the onset of depression. Although a few studies in children and adolescents2,10,11 and adults7,1216 reported persistently abnormal GH secretion patterns after recovery from a depressive episode, these findings could be secondary to the effects of a prior depressive episode (a "scar" effect). What has yet to be examined is whether GH is decreased before the onset of the depression, consistent with its role as a trait marker. Therefore, we evaluated the GH secretion patterns before and after the administration of growth hormone-releasing hormone (GHRH) in children and adolescents who had never been depressed but were at high risk of developing depression. This group was chosen because the best predictor of future development of MDD is a familial history of mood disorders.17,18 Moreover, this strategy has been successfully used to demonstrate the presence of other biological alterations in subjects who had never been depressed but were at high risk for depression.1924

Based on the literature,1,2,17,1924 we hypothesized that subjects at high risk of developing MDD would show a decreased GH response to GHRH stimulation compared with low-risk healthy controls. In addition, since offspring of depressed parents are exposed to more stressful environments when compared with offspring of healthy controls17,18 and since it has been shown that stress may affect GH secretion in humans2527 and animals,2,28 we explored the effects of recent stresses on GH secretion.

SUBJECTS

Sixty-four high-risk and 55 low-risk healthy children and adolescents (mean [SD] age, 10.9 ± 1.7 years) (18 subjects [15%] of the total sample were younger than 12 years) were recruited via advertisement and through parents with mood disorders who attended the outpatient mood disorders clinic. The high-risk subjects were slightly younger, had lower Tanner stage scores, and had lower socioeconomic class compared with the low-risk healthy subjects (Table 1). There were no between-group differences in sex, ethnicity, and body mass index (BMI).

Table Graphic Jump LocationTable 1. Characteristics of High-Risk and Low-Risk Healthy Control Subjects*

Before participating in the study, subjects and their parents were required to sign assents and informed consents, respectively, in compliance with the requirements of the University of Pittsburgh Institutional Review Board.

High-risk subjects were required to have at least 1 first-degree and at least 1 second-degree relative with a history of childhood-onset, recurrent, bipolar, or psychotic depression. In addition, the high-risk subjects were required never to have had a lifetime episode of any mood disorder.

Low-risk healthy subjects were required to have had no lifetime psychiatric disorders; no first-degree relatives with a lifetime episode of any mood or psychotic disorder; no second-degree relatives with a lifetime history of childhood-onset, recurrent, psychotic, or bipolar depression or schizo-affective or schizophrenic disorder; and no more than 20% of second-degree relatives with a lifetime single episode of MDD.

Other exclusionary criteria for both high-risk and low-risk healthy subjects included the use of any medication with central nervous system effects within the past 2 weeks (no subjects were taking serotonin reuptake inhibitors, stimulants, or other antidepressant medications), significant medical illness, extreme obesity (weight greater than 150% of ideal body weight) or growth failure (height or weight below the third percentile), IQ of 70 or less, and inordinate fear of intravenous needles.

MEASUREMENTS

Subjects' lifetime DSM-III-R29 psychiatric symptoms were assessed using the Schedule for Affective Disorders and Schizophrenia for School Aged Children–Epidemiological Version,30 with both the child and parent(s) or guardian(s) serving as informants. Dimensional assessment of symptoms were ascertained using the Child Behavior Checklist.31

To determine familial loading for mood disorders, first- and second-degree relatives were interviewed using the Schedule for Affective Disorders and Schizophrenia for School Aged Children–Epidemiological Version for relatives aged 6 to 18 years and the Schedule for Affective Disorders and Schizophrenia–Lifetime Version32 for adult relatives. Adult first- and second-degree relatives unavailable for direct interview were assessed indirectly using a modified version of the Family History Interview,33 with the child's parent(s) and other available relatives serving as informant(s). All lifetime diagnoses among relatives were made according to the best-estimate procedure34 based on DSM-III-R criteria. All interviews were carried out by trained research clinicians blind to the subject's clinical status under the supervision of the investigators. Interrater reliability for all diagnoses was good (κ≥0.70). Socioeconomic status was measured using the Hollingshead 4-factor index.35

Negative life events that occurred during the year before the interview were assessed using a modified version of the Coddington's Life Events Record.36 Events were classified into those that were dependent on (eg, arguments) or independent (eg, death of a relative) of the child's behavior.36 Current parent-child, peer-child, and mother-father relationships (warmth, tension) and child's school performance were evaluated using the Psychosocial Schedule.37

Tanner stage of sexual development was assessed by the investigators through physical examination using the method described by Marshall and Tanner.38,39 The percentage of agreement for Tanner classification was 90% or higher. For purposes of the analyses, Tanner stage was dichotomized as prepubertal (I/II) or postpubertal (≥III). The BMI was calculated as the weight in kilograms divided by the square of height in meters.

BIOLOGICAL PROCEDURES AND ASSAYS

This study was part of a comprehensive psychobiological investigation of childhood MDD initiated in 1987 by the late Joaquim Puig-Antich, MD, in which other baseline hormones (eg, cortisol), hormonal challenge probes (eg, cortisol and prolactin responses after the administration of 5-hydroxytryptophan), and sleep electroencephalogram were measured with the method described previously.1,2,6,19,40 Briefly, after admission to the Child Sleep Laboratory around 5 PM, an intravenous catheter was placed in an antecubital vein and kept open through a constant drip of isotonic sodium chloride solution. During the first night ("adaptation night"), the catheter was left in place, but no blood was drawn. The next morning, around 9 AM, 3 baseline blood samples for GH were obtained every 15 minutes. Thereafter, subjects were given 1.0 µg/kg of GHRH intravenously for 2 minutes, and blood samples for GH were obtained every 15 minutes for 90 minutes. There were no significant side effects of any kind related to this probe. On the second night, plasma samples for nocturnal baseline GH secretion were drawn every 20 minutes from 9 PM until the subject awoke the following morning.

Blood samples were collected in EDTA tubes and centrifuged, and plasma was stored at −80°C until assayed. The GH radioimmunoassay variability is described elsewhere.1,2,6 Somatostatin was measured only in a subgroup of subjects (high risk, 18; low risk and healthy, 19), using methods similar to Arimura and colleagues,41 on the pooled blood samples collected during sleep. The mean interassay variation of this latter assay was 10.7% coefficient of variation at a spiked value of 50 g/L (range, 42.4-62.0 g/L).

STATISTICAL ANALYSIS

The high-risk and low-risk healthy groups were compared using analysis of variance (ANOVA), χ2 test, and Fisher exact tests as appropriate. The problem of missing data was minimal, with only 0.3% missing. Measurements were examined for normality using the test of Shapiro and the Wilks W statistic. Nonnormally distributed data were normalized using logarithmic transformation. There were no outliers. ANOVA was used to examine the nocturnal GH secretion, the mean GH levels before GHRH administration, and the peak and mean GH levels after GHRH administration. Regression analyses were used to test effects of group status on GH secretion after the administration of GHRH, adjusting for pre-GHRH GH baseline levels, age, sex, BMI, Tanner stage, socioeconomic status, and their interactions. Correlations between cortisol, somatostatin, family loading for mood disorders, and negative events with GH secretion were analyzed using Pearson or Spearman correlations. All values are reported as mean ± SD. All P values are based on 2-tailed tests with a 2-tailed α of .05.

Before analyzing the between-group differences for GH secretion, the correlations among demographic characteristics, Tanner stage, BMI, and GH secretion patterns were examined. Both age and BMI were negatively correlated with GH secretion after GHRH administration (r = −0.16 to −0.41, P≤.05). Both BMI and Tanner stage were negatively correlated with nocturnal GH secretion (r = −0.35, P = .001; r = −0.21, P = .03, respectively). Therefore, these characteristics, as well as sex, were controlled for in all statistical analyses.

All subjects participated in the GHRH stimulation probe. However, due to methodologic problems (eg, intravenous catheter problems), only 57 high-risk and 48 low-risk healthy subjects were included for the nocturnal GH secretion analyses. There were no significant demographic, Tanner stage, and BMI differences between subjects whose data were and were not included in the nocturnal GH studies.

Within the high-risk group, 21 subjects (33%) had 1 or more of the following lifetime nonaffective psychiatric disorders: oppositional defiant disorder (10 subjects), attention-deficit/hyperactive disorder (13 subjects), or separation anxiety disorder (2 subjects with disruptive disorder). Compared with the high-risk subjects without psychiatric disorders, the high-risk subjects with psychiatric disorders had lower socioeconomic status (38.7 ± 10.8 [class III]35 vs 45.6 ± 12.9 [class IV],35t62 = 2.10, P = .04) and were more likely to be African American (14.3% vs 0.0%, Fisher exact test, P = .03). There were no age, sex, Tanner stage, or BMI differences between the high-risk subjects with or without psychiatric disorders. Therefore, the analyses of the results were performed with and without the subjects with nonaffective psychiatric disorders.

There were no significant differences in the GH levels between the high-risk and low-risk healthy subjects before the administration of GHRH (Table 2). After the administration of GHRH, the high-risk and low-risk healthy controls showed increased secretion of GH, but the magnitude of the increase was markedly less in the high-risk group (Figure 1, Table 2). Adjusting for age, sex, BMI, Tanner stage, and their interactions, the high-risk subjects still showed significantly lower mean and peak GH than the low-risk healthy controls (effect sizes for mean and peak GH levels, 0.52 [P = .007] and 0.40 [P = .04], respectively). These results were unchanged after controlling for the pre-GHRH baseline GH levels.

Table Graphic Jump LocationTable 2. Growth Hormone (GH) After Growth Hormone-Releasing Hormone (GHRH) and Nocturnal GH Secretion in High-Risk and Low-Risk Healthy Subjects*
Place holder to copy figure label and caption

Growth hormone (GH) response to growth hormone-releasing hormone (GHRH).

Graphic Jump Location

To evaluate whether the high-risk subjects with psychiatric disorders accounted for the between-group differences, we repeated these analyses, excluding the high-risk subjects with psychiatric disorders. High-risk subjects without psychiatric disorders continued to show significantly lower GH response to GHRH infusion compared with the low-risk healthy subjects (adjusted mean, 7.9 ± 1.3 µg/L vs 12.5 ± 1.2 µg/L, t113 = 2.75, P = .007, effect size = 0.58; adjusted peak, 13.8 ± 2.2 µg/L vs 20.2 ± 1.9 µg/L, t113 = 2.23, P = .03, effect size = 0.46). Moreover, there were no significant differences in any GH variable between the high-risk subjects with and without psychiatric disorders.

There were no significant group differences between the high-risk and low-risk healthy subjects in the nocturnal mean GH secretion level, even after adjusting for the effects of age, sex, BMI, and Tanner stage (Table 2). Since most studies of MDD across ages have reported alterations in GH during the first 3 hours of sleep,7,16,42,43 we restricted our analyses of GH secretion of the high-risk vs low-risk healthy groups to this period and failed to find any differences.

There were no significant differences in the nocturnal GH secretion among the high-risk subjects without psychiatric disorders (n = 39), the high-risk subjects with psychiatric disorders (n = 18), and the low-risk healthy controls (n = 48) (3.6 ± 2.7 µg/L vs 3.2 ± 2.6 µg/L vs 3.5 ± 2.7 µg/L, respectively; F2,102 = 0.93, P = .4).

There were no significant correlations between dimensional measures of anxiety and depression (measured by the Child Behavior Checklist) and GH secretion patterns (ρ = 0.03-0.14, P = .23-.76).

Since somatostatin and cortisol inhibit the release of GH,44 we explored the effects of these hormones on GH variables. Somatostatin showed a nonsignificant negative correlation with nocturnal GH secretion (ρ = −0.16, P = .33) and, contrary to our expectations, was positively correlated with the mean and peak GH secretion after GHRH (r = 0.44 [P = .003] and r = 0.37 [P = .01], respectively). In contrast, no significant correlations were found between any GH variables and cortisol secretion (ρ = −0.10 to 0.16, P = .2-.03).

There were no significant correlations among the total, independent, and dependent negative life events and family and peer relationships with the GH measurements (ρ = −0.13 to 0.05, P = .11-.5). There were no significant differences in GH secretion between subjects living with both parents compared with those living with only 1 parent (P = .14-.97).

There were no significant associations between the family loading for anxiety disorders and any GH variable (for the mean and peak GH response to GHRH, F1,114 = 0.98 [P = .32] and 0.28 [P = .6], respectively). By definition, the high-risk subjects had high family loading for lifetime mood disorders. Therefore, the overall effects of family loading for mood disorders could not be examined. However, we were able to explore the effects of living with a mother with lifetime MDD (n = 52) vs no MDD (n = 13), a father with lifetime MDD (n = 25) vs no MDD (n = 40), and living with both parents with MDD (n = 20) vs no parents with lifetime MDD (n = 8) within the high-risk subjects. No significant findings for any GH variable were found based on parental lifetime mood disorders.

In this study, we found that after stimulation with GHRH children and adolescents at high risk of developing MDD secreted significantly less GH compared with the low-risk healthy controls. There were no between-group differences in the baseline GH secretion levels before GHRH administration and nocturnal GH secretion. Also, there were no effects of cortisol, somatostatin, family loading for anxiety disorders, recent environmental stressors, and living with 1 or both parent(s) on any GH measurement. However, high-risk children and adolescents showed a similar degree of blunted GH response to GHRH to already depressed children and adolescents also studied in our laboratory2 (mean GH response, 8.6 ± 1.1 µg/L vs 8.7 ± 0.9 µg/L; peak GH response, 15.2 ± 1.8 µg/L vs 13.8 ± 1.4 µg/L). These findings, together with the decreased GH levels after GHRH administration found in acutely depressed patients across the age span14 and after recovery from depression,2,7,1016 suggest that the dysregulation of the GH response to GHRH might be a trait marker that antedates the onset of a depressive episode. To prove this hypothesis, longitudinal clinical follow-up of the high-risk subjects with low and normal GH responses to GHRH is warranted.

Before considering the implications of this study, it is important to emphasize that our results need to be considered in light of the following limitations. Because only 15% of the sample were adolescents, our results pertain mainly to prepubertal children. The instruments used to evaluate the effects of environmental stressors on the GH secretion may not have been sufficiently sensitive27,36 and only assessed recent stressors. Finally, peripheral measures of somatostatin and cortisol do not necessarily reflect the activity of these substances in the brain.

The mechanisms by which the GH response to GHRH is decreased in children and adolescents at high risk of developing depression are not clear. The neurotransmitter systems that have been associated with the pathogenesis of MDD17,40 have also been implicated, at least in part, in the regulation of GH28,4446 and the pathogenesis of depression-like symptoms in animals.28,4750 Studies in children25,26,51,52 and both young and mature animals44,5358 exposed to stress have shown abnormal basal GH secretion and decreased GH secretion in response to stimulation that appear to be partially mediated by central serotonergic and noradrenergic mechanisms.28,44,46,50,5658 In contrast with the persistent reduction in GH secretion after stimulation found in subjects who had recovered from depression across the life span,2,7,1016 the biological changes triggered by stress appear to be reversible when the stress is removed (eg, the child is placed in a supportive environment25,26,59 or the animal is returned to the mother28,46,50,59,60) or in animals when antidepressants have been administered.47,48,61,62 However, some animals appear to show long-term changes in behavior and neuroendocrine response to exposure to early stresses into adulthood,28,53,62 which may, in part, be genetically mediated.53,63 In our study, we did not find any effects of recent stresses on the secretion of GH, but it is possible that the high-risk subjects may have been exposed to events that occurred before the time in which the stresses were measured in this study (eg, abuse).

Other studies have also shown that infants, children, and adolescents who had never been depressed but who are at high risk of developing MDD present biological abnormalities,1924 including changes in cortisol and prolactin secretion after the administration of 5-hydroxytryptophan,19 similar sleep architecture abnormalities as their depressed parents,22 and left-right brain frontal hemisphere asymmetry on their electroencephalograms.20,21,24 Also, adult subjects without prior depressive episodes but with a family history of MDD have been reported to have a greater worsening in mood after tryptophan depletion compared with those without positive family histories,64 low cerebrospinal fluid 5-hydroxyindoleacetic acid levels,65,66 altered hypothalamic-pituitary-adrenal responses,23 and sleep electroencephalographic abnormalities.67 Some of these biological abnormalities appear to be markers not only for the risk to develop depression but also for recurrences of depression among adolescents68 and adults,69,70 emphasizing the importance of biological studies in populations at high risk of developing psychiatric disorders.

In summary, children and adolescents at high risk for depression showed decreased GH secretion after GHRH administration compared with low-risk healthy controls, which parallels the findings among children and adolescents with an acute episode of MDD and after recovery.1,2,10,11 The results of this study suggest that decreased GH response to GHRH may be a trait marker for MDD and that the mechanisms that control the secretion of GH may be already altered before the first depressive episode. Ongoing follow-up of subjects included in this study will help clarify whether decreased GH response to GHRH, maturational development, and ongoing exposure to stress separately or together predict the development of first-onset MDD. Differentiating between a genetic basis for this trait vs a marker of early stress in these families warrants further study.

Accepted for publication April 11, 2000.

This work was supported by National Institute of Mental Health (Rockville, Md) grant MH41712 (initially to Dr Puig-Antich and then to Dr Ryan and colleagues).

This article is dedicated to Dr Puig-Antich's memory.

We extend our appreciation to the sleep/neuroendocrine staff, clinical interviewers, members of the data analytic core, and the families who made this study possible. We also extend our appreciation to Therese Deiseroth and Carol Kostek for editorial assistance with the manuscript.

Corresponding author: Boris Birmaher, MD, Western Psychiatric Institute and Clinic, 3811 O'Hara St, Pittsburgh, PA 15213 (e-mail: birmaherb@msx.upmc.edu).

Ryan  NDDahl  REPerel  JBirmaher  BWilliamson  DIyengar  SNelson  BPuig-Antich  JPerel  JM Stimulatory tests of growth hormone secretion in prepubertal major depression: depressed versus normal children. J Am Acad Child Adolesc Psychiatry. 1994;33824- 833
Link to Article
Dahl  RBirmaher  BWilliamson  DEPerel  JKaufman  JDorn  LAxelson  DDeBellis  MRyan  ND The regulation of growth hormone in depressed children: comparison with controls, episode versus recovery, and reliability studies. Biol Psychiatry. In press
Dinan  TG Psychoneuroendocrinology of depression: growth hormone. Psychiatr Clin North Am. 1998;21325- 339
Link to Article
Krishnan  KRManepalli  ANRitchie  JCRayasam  KMelville  MLDaughtry  GThorner  MORivier  JEVale  WWNemeroff  CB Growth hormone-releasing factor stimulation test in depression. Am J Psychiatry. 1988;14590- 92
Dahl  RERyan  NDWilliamson  DEAmbrosini  PJRabinovich  HNovacenko  HNelson  BPuig-Antich  J Regulation of sleep and growth hormone in adolescent depression. J Am Acad Child Adolesc Psychiatry. 1992;31615- 621
Link to Article
DeBellis  MDDahl  REPerel  JBirmaher  BAl-Shabbout  MWilliamson  DENelson  BRyan  ND Nocturnal ACTH cortisol, growth hormone, and prolactin secretion in prepubertal depression. J Am Acad Child Adolesc Psychiatry. 1996;351130- 1138
Link to Article
Jarrett  DBMiewald  JMKupfer  DJ Recurrent depression is associated with a persistent reduction in sleep-related growth hormone secretion. Arch Gen Psychiatry. 1990;47113- 118
Link to Article
Kutcher  SMalkin  DSilverberg  JMarton  PWilliamson  PMalkin  ASzalai  JKatic  M Nocturnal cortisol, thyroid stimulating hormone, and growth hormone secretory profiles in depressed adolescents. J Am Acad Child Adolesc Psychiatry. 1991;30407- 414
Link to Article
Sakkas  PNSoldatos  CRBergiannaki  JDPaparrigopoulos  TJStefanis  CW Growth hormone secretion during sleep in male depressed patients. Prog Neuropsychopharmacol Biol Psychiatry. 1998;22467- 483
Link to Article
Puig-Antich  JNovacenko  HDavies  MTabrizi  MAAmbrosini  PGoetz  RBianca  JGoetz  DSachar  EJ Growth hormone secretion in prepubertal children with major depression, III: response to insulin-induced hypoglycemia after recovery from a depressive episode and in a drug-free state. Arch Gen Psychiatry. 1984;41471- 475
Link to Article
Puig-Antich  JGoetz  RDavies  MTabrizi  MANovacenko  HHanlon  CSachar  EJWeitzman  E Growth hormone secretion in prepubertal children with major depression, IV: sleep-related plasma concentrations in a drug-free, fully recovered clinical state. Arch Gen Psychiatry. 1984;41479- 483
Link to Article
Mitchell  PBBearn  JACorn  THCheckley  SA Growth hormone response to clonidine after recovery in patients with endogenous depression. Br J Psychiatry. 1988;15234- 38
Link to Article
Siever  LJTrestman  RLCoccaro  EF The growth hormone response to clonidine in acute and remitted depressed male patients. Neuropsychopharmacology. 1992;6165- 177
Steiger  Avon Bardeleben  UGuldner  JLauer  CRothe  BHolsboer  F The sleep EEG and nocturnal hormone secretion studies on changes during the course of depression and on effects of CNS-active drugs. Prog Neuropsychopharmacol Biol Psychiatry. 1993;17125- 137
Link to Article
Charney  DSHeninger  GRSternberg  DE Failure of chronic antidepressant treatment to alter growth hormone response to clonidine. Psychiatry Res. 1982;7135- 138
Link to Article
Jarrett  DBKupfer  DJMiewald  JMGrochocinski  VJFranz  B Sleep-related growth hormone secretion is persistently suppressed in women with recurrent depression: a preliminary longitudinal analysis. J Psychiatr Res. 1994;28211- 223
Link to Article
Birmaher  BRyan  NDWilliamson  DBrent  DKaufman  JDahl  RPerel  JNelson  B Childhood and adolescent depression: a review of the past 10 years, part I. J Am Acad Child Adolesc Psychiatry. 1996;351427- 1439
Link to Article
Beardslee  WRVersage  EMGladstone  TRG Children of affectively ill parents: a review of the past 10 years. J Am Acad Child Adolesc Psychiatry. 1998;371134- 1141
Link to Article
Birmaher  BKaufman  JBrent  DADahl  REPerel  JMAl-Shabbout  MNelson  BStull  SRao  UWaterman  GSWilliamson  DERyan  ND Neuroendocrine response to 5-hydroxy-L-tryptophan in prepubertal children at high risk of major depressive disorder. Arch Gen Psychiatry. 1997;541113- 1119
Link to Article
Dawson  GFrey  KPanagiotides  HOsterling  JHessl  D Infants of depressed mothers exhibit atypical frontal brain activity: a replication and extension of previous findings. J Child Psychol Psychiatry. 1997;38179- 186
Link to Article
Field  TPickens  JFox  NAGonzalez  JNawrocki  T Facial expression and EEG responses to happy and sad faces/voices by 3-month-old infants of depressed mothers. Br J Dev Psychol. 1998;16485- 494
Link to Article
Giles  DERoffwarg  HPDahl  REKupfer  DJ Electroencephalographic sleep abnormalities in depressed children: a hypothesis. Psychiatry Res. 1992;4153- 63
Link to Article
Holsboer  FLauer  CJSchreiber  WKrieg  JC Altered hypothalamic-pituitary-adrenocortical regulation in healthy subjects at high familial risk for affective disorders. Neuroendocrinology. 1995;62340- 347
Link to Article
Jones  NAField  TFox  NADavalos  MLundy  BHart  S Newborns of mothers with depressive symptoms are physiologically less developed. Infant Behav Dev. 1998;21537- 541
Link to Article
Gardner  LI Deprivation dwarfism. Sci Am. 1972;22776- 83
Link to Article
Powell  GFBrasel  JARaiti  SBlizzard  RM Emotional deprivation and growth retardation stimulating idiopathic hypopituitarism, II: endocrinologic evaluation of the syndrome. N Engl J Med. 1967;2761279- 1283
Link to Article
Williamson  DEBirmaher  BDahl  REAl-Shabbout  MRyan  ND Stressful life events influence nocturnal growth hormone secretion in depressed children. Biol Psychiatry. 1996;401176- 1180
Link to Article
Kuhn  CMSchanberg  SM Responses to maternal separation: mechanisms and mediators. Int J Dev Neurosci. 1998;16261- 270
Link to Article
American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders Revised Third Edition Washington, DC American Psychiatric Association1987;
Orvachel  HPuig-Antich  JChambers  WJTabrizi  MAJohnson  R Retrospective assessment of child psychopathology with the K-SADS-E. J Am Acad Child Psychiatry. 1982;21392- 397
Link to Article
Achenbach  TMEdelbrock  C Manual for the Child Behavior Checklist and Revised Child Behavior Profile.  Burlington University of Vermont, Dept of Psychiatry1983;
Endicott  JSpitzer  RL A Diagnostic Interview: the Schedule for Affective Disorders and Schizophrenia. Arch Gen Psychiatry. 1978;35837- 844
Link to Article
Weissman  MWarner  VWickramaratne  PMoreau  DOlfson  M Offspring of depressed parents: 10 years later. Arch Gen Psychiatry. 1997;54932- 940
Link to Article
Leckman  JFSholomskas  DThompson  WDBelanger  AWeissman  MM Best estimate of lifetime psychiatric diagnosis: a methodological study. Arch Gen Psychiatry. 1982;39879- 883
Link to Article
Hollingshead  AB Four-Factor Index of Social Status.  New Haven, Conn Yale University, Department of Sociology1975;
Williamson  DEBirmaher  BAnderson  BPAl-Shabbout  MRyan  ND Stressful life events in depressed adolescents: the role of dependent events during the depressive episode. J Am Acad Child Adolesc Psychiatry. 1995;34591- 598
Link to Article
Puig-Antich  JKaufman  JRyan  NDWilliamson  DEDahl  RELukens  ETodak  GAmbrosini  PRabinovich  HNelson  B The psychosocial functioning and family environment of depressed adolescents. J Am Acad Child Adolesc Psychiatry. 1993;32244- 253
Link to Article
Marshall  WTanner  JM Variations in pattern of pubertal changes in girls. Arch Dis Child. 1969;44291- 293
Link to Article
Marshall  WATanner  JM Variations in pattern of pubertal changes in boys. Arch Dis Child. 1970;4513- 23
Link to Article
Birmaher  BRyan  ND Neurobiological factors in depressed children and adolescents. Essau  CAPetermann  Feds.Depressive Disorders in Children and Adolescents Epidemiology, Risk Factors, and Treatment. Northvale, NJ Jason Aronson Inc Publishers1999;
Arimura  ALudqvist  GRothman  JChang  RFernandez-Durango  RElde  RCoy  DHMeyers  CSchally  AV Radioimmunoassay of somatostatin. Metabolism. 1978;271139- 1144
Link to Article
Puig-Antich  JGoetz  RDavies  MFein  MHanlon  CChambers  WJTabrizi  MASachar  EJWeitzman  ED Growth hormone secretion in prepubertal children with major depression, II: sleep-related plasma concentrations during a depressive episode. Arch Gen Psychiatry. 1984;41463- 466
Link to Article
Sakkas  PNSoldatos  CRBergiannaki  JDPaparrigopoulos  TJStefanis  CN Growth hormone secretion during sleep in male depressed patients. Prog Neuropsychopharmacol Biol Psychiatry. 1998;22467- 483
Link to Article
Muller  EELocatelli  VCocchi  D Neuroendocrine control of growth hormone secretion. Physiol Rev. 1999;79511- 607
Mota  ABento  APenalva  APomba  MDieguez  C Role of serotonin receptor subtype 5-HT(ID) on basal and stimulated growth hormone secretion. J Clin Endocrinol Metab. 1995;801973- 1977
Katz  LMNathan  LKuhn  CMSchanberg  SM Inhibition of GH in maternal separation may be mediated through altered serotonergic activity at 5-HT(2A) and 5-HT(2C) receptors. Psychoneuroendocrinology. 1996;21219- 235
Link to Article
Aulakh  CSMazzola-Pomietto  PMurphy  DL Long-term antidepressant treatment restores clonidine's effect on growth secretion in a genetic animal model of depression. Pharmacol Biochem Behav. 1996;55265- 268
Link to Article
Moreau  JLJenck  FMartin  JRPerrin  SHaefely  WE Effects of repeated mild stress and two antidepressant treatments on the behavioral response to 5HT1C receptor activation in rats. Psychopharmacology. 1993;110140- 144
Link to Article
Zangen  AOverstreet  DHYadid  G High serotonin and 5-hydroxyindoleacetic acid levels in limbic brain regions in a rat model of depression: normalization by chronic antidepressant treatment. J Neurochem. 1997;692477- 2483
Link to Article
Suomi  SJ Early determinants of behavior: evidence from primate studies. Br Med Bull. 1997;53170- 184
Link to Article
DeBellis  MDChrousos  GPDorn  LDBurke  LHelmers  KKling  MATrickett  PKPutnam  FW Hypothalamic-pituitary-adrenal axis dysregulation in sexually abused girls. J Clin Endocrinol Metab. 1994;78249- 255
Frasier  SDRallison  ML Growth retardation and emotional deprivation: relative resistance to treatment with human growth hormone. J Pediatr. 1972;80603- 609
Link to Article
Anisman  HZaharia  MDMeaney  MJMerali  Z Do early-life events permanently alter behavioral and hormonal responses to stressors? Int J Dev Neurosci. 1998;16149- 164
Link to Article
Van Oers  HJJde Kloet  ERLevine  S Early vs. late maternal deprivation differentially alters the endocrine and hypothalamic responses to stress. Brain Res Dev Brain Res. 1998;111245- 252
Link to Article
Rosenblum  LACoplan  JDFriedman  SBassoff  TGorman  JMAndrews  MW Adverse early experiences affect noradrenergic and serotonergic functioning in adult primates. Biol Psychiatry. 1994;35221- 227
Link to Article
Laudenslager  MLBoccia  MLBerger  CLGennaro-Ruggles  MMMcFerran  BReite  ML Total cortisol, free cortisol, and growth hormone associated with brief social separation experiences in young macaques. Dev Psychobiol. 1995;28199- 211
Link to Article
Kuhn  CMPauk  JSchanberg  SM Endocrine responses to mother-infant separation in developing rats. Dev Psychobiol. 1990;23395- 410
Link to Article
Coplan  JDTrost  RCOwens  MJCooper  TBGorman  JMNemeroff  CBRosenblum  LA Cerebrospinal fluid concentrations of somatostatin and biogenic amines in grown primates reared by mothers exposed to manipulated foraging conditions. Arch Gen Psychiatry. 1998;55473- 477
Link to Article
Pauk  JKuhn  CMField  TMSchanberg  SM Positive effects of tactile vs. kinesthetic or vestibular stimulation on neuroendocrine and ODC activity in maternally deprived rat pups. Life Sci. 1986;392081- 2087
Link to Article
Field  TMSchanberg  SMScafidi  FBauer  CRVega-Lahr  NGracia  RNystrom  JKuhn  CM Effects of tactile/kinesthetic stimulation in pre-term neonates. Pediatrics. 1986;77654- 658
Suomi  SJSeaman  SFLewis  JK Effects of imipramine treatment of separation-induced social disorder in rhesus monkeys. Arch Gen Psychiatry. 1978;35321- 325
Link to Article
Ladd  COOwens  MJNemeroff  CB Persistent changes in corticotropin-releasing factor neuronal systems induced by maternal deprivation. Endocrinology. 1996;1371212- 1218
Higley  JDThompson  WWChampoux  MGoldman  DHasert  MFKraemer  GWScanlan  JMSuomi  SJLinnoila  M Paternal and maternal genetic and environmental contributions to cerebrospinal fluid monamine metabolites in rhesus monkeys (Macaca mullatta). Arch Gen Psychiatry. 1993;50615- 623
Link to Article
Benkelfat  CEllenbogen  MADean  PPalmour  RMYoung  SN Mood-lowering effect of tryptophan depletion: enhanced susceptibility of young men at genetic risk for major affective disorders. Arch Gen Psychiatry. 1994;51687- 697
Link to Article
Sedvall  GFyro  BGullberg  BNyback  HWiesel  FAWode-Helgodt  B Relationships in healthy volunteers between concentrations of monoamine metabolites in cerebrospinal fluid and family history of psychiatric morbidity. Br J Psychiatry. 1980;136366- 374
Link to Article
Rosenthal  NEDavenport  YCowdry  RWWebster  MHGoodwin  FK Monoamine metabolites in cerebrospinal fluid of depressive subtypes. Psychiatry Res. 1980;2113- 119
Link to Article
Lauer  CJSchreiber  WHolsboer  FKrieg  JC In quest of identifying vulnerability markers for psychiatric disorders by all-night polysomnography. Arch Gen Psychiatry. 1995;52145- 153
Link to Article
Rao  UDahl  RERyan  NDBirmaher  BWilliamson  DERao  RKaufman  JNelson  B The relationship between longitudinal clinical course and sleep and cortisol changes in adolescent depression. Biol Psychiatry. 1996;40474- 484
Link to Article
Franz  BKupfer  DJMiewald  JMJarrett  DBGrochocinski  VJ Growth hormone secretion timing in depression: clinical outcome comparisons. Biol Psychiatry. 1995;38720- 729
Link to Article
Thase  MEKupfer  DJBuysse  DJFrank  ESimons  ADMcEachran  ABRashid  KFGrochocinski  VJ Electroencephalographic sleep profiles in single-episode and recurrent unipolar forms of major depression, I: comparison during acute depressive states. Biol Psychiatry. 1995;38506- 515
Link to Article

Figures

Place holder to copy figure label and caption

Growth hormone (GH) response to growth hormone-releasing hormone (GHRH).

Graphic Jump Location

Tables

Table Graphic Jump LocationTable 1. Characteristics of High-Risk and Low-Risk Healthy Control Subjects*
Table Graphic Jump LocationTable 2. Growth Hormone (GH) After Growth Hormone-Releasing Hormone (GHRH) and Nocturnal GH Secretion in High-Risk and Low-Risk Healthy Subjects*

References

Ryan  NDDahl  REPerel  JBirmaher  BWilliamson  DIyengar  SNelson  BPuig-Antich  JPerel  JM Stimulatory tests of growth hormone secretion in prepubertal major depression: depressed versus normal children. J Am Acad Child Adolesc Psychiatry. 1994;33824- 833
Link to Article
Dahl  RBirmaher  BWilliamson  DEPerel  JKaufman  JDorn  LAxelson  DDeBellis  MRyan  ND The regulation of growth hormone in depressed children: comparison with controls, episode versus recovery, and reliability studies. Biol Psychiatry. In press
Dinan  TG Psychoneuroendocrinology of depression: growth hormone. Psychiatr Clin North Am. 1998;21325- 339
Link to Article
Krishnan  KRManepalli  ANRitchie  JCRayasam  KMelville  MLDaughtry  GThorner  MORivier  JEVale  WWNemeroff  CB Growth hormone-releasing factor stimulation test in depression. Am J Psychiatry. 1988;14590- 92
Dahl  RERyan  NDWilliamson  DEAmbrosini  PJRabinovich  HNovacenko  HNelson  BPuig-Antich  J Regulation of sleep and growth hormone in adolescent depression. J Am Acad Child Adolesc Psychiatry. 1992;31615- 621
Link to Article
DeBellis  MDDahl  REPerel  JBirmaher  BAl-Shabbout  MWilliamson  DENelson  BRyan  ND Nocturnal ACTH cortisol, growth hormone, and prolactin secretion in prepubertal depression. J Am Acad Child Adolesc Psychiatry. 1996;351130- 1138
Link to Article
Jarrett  DBMiewald  JMKupfer  DJ Recurrent depression is associated with a persistent reduction in sleep-related growth hormone secretion. Arch Gen Psychiatry. 1990;47113- 118
Link to Article
Kutcher  SMalkin  DSilverberg  JMarton  PWilliamson  PMalkin  ASzalai  JKatic  M Nocturnal cortisol, thyroid stimulating hormone, and growth hormone secretory profiles in depressed adolescents. J Am Acad Child Adolesc Psychiatry. 1991;30407- 414
Link to Article
Sakkas  PNSoldatos  CRBergiannaki  JDPaparrigopoulos  TJStefanis  CW Growth hormone secretion during sleep in male depressed patients. Prog Neuropsychopharmacol Biol Psychiatry. 1998;22467- 483
Link to Article
Puig-Antich  JNovacenko  HDavies  MTabrizi  MAAmbrosini  PGoetz  RBianca  JGoetz  DSachar  EJ Growth hormone secretion in prepubertal children with major depression, III: response to insulin-induced hypoglycemia after recovery from a depressive episode and in a drug-free state. Arch Gen Psychiatry. 1984;41471- 475
Link to Article
Puig-Antich  JGoetz  RDavies  MTabrizi  MANovacenko  HHanlon  CSachar  EJWeitzman  E Growth hormone secretion in prepubertal children with major depression, IV: sleep-related plasma concentrations in a drug-free, fully recovered clinical state. Arch Gen Psychiatry. 1984;41479- 483
Link to Article
Mitchell  PBBearn  JACorn  THCheckley  SA Growth hormone response to clonidine after recovery in patients with endogenous depression. Br J Psychiatry. 1988;15234- 38
Link to Article
Siever  LJTrestman  RLCoccaro  EF The growth hormone response to clonidine in acute and remitted depressed male patients. Neuropsychopharmacology. 1992;6165- 177
Steiger  Avon Bardeleben  UGuldner  JLauer  CRothe  BHolsboer  F The sleep EEG and nocturnal hormone secretion studies on changes during the course of depression and on effects of CNS-active drugs. Prog Neuropsychopharmacol Biol Psychiatry. 1993;17125- 137
Link to Article
Charney  DSHeninger  GRSternberg  DE Failure of chronic antidepressant treatment to alter growth hormone response to clonidine. Psychiatry Res. 1982;7135- 138
Link to Article
Jarrett  DBKupfer  DJMiewald  JMGrochocinski  VJFranz  B Sleep-related growth hormone secretion is persistently suppressed in women with recurrent depression: a preliminary longitudinal analysis. J Psychiatr Res. 1994;28211- 223
Link to Article
Birmaher  BRyan  NDWilliamson  DBrent  DKaufman  JDahl  RPerel  JNelson  B Childhood and adolescent depression: a review of the past 10 years, part I. J Am Acad Child Adolesc Psychiatry. 1996;351427- 1439
Link to Article
Beardslee  WRVersage  EMGladstone  TRG Children of affectively ill parents: a review of the past 10 years. J Am Acad Child Adolesc Psychiatry. 1998;371134- 1141
Link to Article
Birmaher  BKaufman  JBrent  DADahl  REPerel  JMAl-Shabbout  MNelson  BStull  SRao  UWaterman  GSWilliamson  DERyan  ND Neuroendocrine response to 5-hydroxy-L-tryptophan in prepubertal children at high risk of major depressive disorder. Arch Gen Psychiatry. 1997;541113- 1119
Link to Article
Dawson  GFrey  KPanagiotides  HOsterling  JHessl  D Infants of depressed mothers exhibit atypical frontal brain activity: a replication and extension of previous findings. J Child Psychol Psychiatry. 1997;38179- 186
Link to Article
Field  TPickens  JFox  NAGonzalez  JNawrocki  T Facial expression and EEG responses to happy and sad faces/voices by 3-month-old infants of depressed mothers. Br J Dev Psychol. 1998;16485- 494
Link to Article
Giles  DERoffwarg  HPDahl  REKupfer  DJ Electroencephalographic sleep abnormalities in depressed children: a hypothesis. Psychiatry Res. 1992;4153- 63
Link to Article
Holsboer  FLauer  CJSchreiber  WKrieg  JC Altered hypothalamic-pituitary-adrenocortical regulation in healthy subjects at high familial risk for affective disorders. Neuroendocrinology. 1995;62340- 347
Link to Article
Jones  NAField  TFox  NADavalos  MLundy  BHart  S Newborns of mothers with depressive symptoms are physiologically less developed. Infant Behav Dev. 1998;21537- 541
Link to Article
Gardner  LI Deprivation dwarfism. Sci Am. 1972;22776- 83
Link to Article
Powell  GFBrasel  JARaiti  SBlizzard  RM Emotional deprivation and growth retardation stimulating idiopathic hypopituitarism, II: endocrinologic evaluation of the syndrome. N Engl J Med. 1967;2761279- 1283
Link to Article
Williamson  DEBirmaher  BDahl  REAl-Shabbout  MRyan  ND Stressful life events influence nocturnal growth hormone secretion in depressed children. Biol Psychiatry. 1996;401176- 1180
Link to Article
Kuhn  CMSchanberg  SM Responses to maternal separation: mechanisms and mediators. Int J Dev Neurosci. 1998;16261- 270
Link to Article
American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders Revised Third Edition Washington, DC American Psychiatric Association1987;
Orvachel  HPuig-Antich  JChambers  WJTabrizi  MAJohnson  R Retrospective assessment of child psychopathology with the K-SADS-E. J Am Acad Child Psychiatry. 1982;21392- 397
Link to Article
Achenbach  TMEdelbrock  C Manual for the Child Behavior Checklist and Revised Child Behavior Profile.  Burlington University of Vermont, Dept of Psychiatry1983;
Endicott  JSpitzer  RL A Diagnostic Interview: the Schedule for Affective Disorders and Schizophrenia. Arch Gen Psychiatry. 1978;35837- 844
Link to Article
Weissman  MWarner  VWickramaratne  PMoreau  DOlfson  M Offspring of depressed parents: 10 years later. Arch Gen Psychiatry. 1997;54932- 940
Link to Article
Leckman  JFSholomskas  DThompson  WDBelanger  AWeissman  MM Best estimate of lifetime psychiatric diagnosis: a methodological study. Arch Gen Psychiatry. 1982;39879- 883
Link to Article
Hollingshead  AB Four-Factor Index of Social Status.  New Haven, Conn Yale University, Department of Sociology1975;
Williamson  DEBirmaher  BAnderson  BPAl-Shabbout  MRyan  ND Stressful life events in depressed adolescents: the role of dependent events during the depressive episode. J Am Acad Child Adolesc Psychiatry. 1995;34591- 598
Link to Article
Puig-Antich  JKaufman  JRyan  NDWilliamson  DEDahl  RELukens  ETodak  GAmbrosini  PRabinovich  HNelson  B The psychosocial functioning and family environment of depressed adolescents. J Am Acad Child Adolesc Psychiatry. 1993;32244- 253
Link to Article
Marshall  WTanner  JM Variations in pattern of pubertal changes in girls. Arch Dis Child. 1969;44291- 293
Link to Article
Marshall  WATanner  JM Variations in pattern of pubertal changes in boys. Arch Dis Child. 1970;4513- 23
Link to Article
Birmaher  BRyan  ND Neurobiological factors in depressed children and adolescents. Essau  CAPetermann  Feds.Depressive Disorders in Children and Adolescents Epidemiology, Risk Factors, and Treatment. Northvale, NJ Jason Aronson Inc Publishers1999;
Arimura  ALudqvist  GRothman  JChang  RFernandez-Durango  RElde  RCoy  DHMeyers  CSchally  AV Radioimmunoassay of somatostatin. Metabolism. 1978;271139- 1144
Link to Article
Puig-Antich  JGoetz  RDavies  MFein  MHanlon  CChambers  WJTabrizi  MASachar  EJWeitzman  ED Growth hormone secretion in prepubertal children with major depression, II: sleep-related plasma concentrations during a depressive episode. Arch Gen Psychiatry. 1984;41463- 466
Link to Article
Sakkas  PNSoldatos  CRBergiannaki  JDPaparrigopoulos  TJStefanis  CN Growth hormone secretion during sleep in male depressed patients. Prog Neuropsychopharmacol Biol Psychiatry. 1998;22467- 483
Link to Article
Muller  EELocatelli  VCocchi  D Neuroendocrine control of growth hormone secretion. Physiol Rev. 1999;79511- 607
Mota  ABento  APenalva  APomba  MDieguez  C Role of serotonin receptor subtype 5-HT(ID) on basal and stimulated growth hormone secretion. J Clin Endocrinol Metab. 1995;801973- 1977
Katz  LMNathan  LKuhn  CMSchanberg  SM Inhibition of GH in maternal separation may be mediated through altered serotonergic activity at 5-HT(2A) and 5-HT(2C) receptors. Psychoneuroendocrinology. 1996;21219- 235
Link to Article
Aulakh  CSMazzola-Pomietto  PMurphy  DL Long-term antidepressant treatment restores clonidine's effect on growth secretion in a genetic animal model of depression. Pharmacol Biochem Behav. 1996;55265- 268
Link to Article
Moreau  JLJenck  FMartin  JRPerrin  SHaefely  WE Effects of repeated mild stress and two antidepressant treatments on the behavioral response to 5HT1C receptor activation in rats. Psychopharmacology. 1993;110140- 144
Link to Article
Zangen  AOverstreet  DHYadid  G High serotonin and 5-hydroxyindoleacetic acid levels in limbic brain regions in a rat model of depression: normalization by chronic antidepressant treatment. J Neurochem. 1997;692477- 2483
Link to Article
Suomi  SJ Early determinants of behavior: evidence from primate studies. Br Med Bull. 1997;53170- 184
Link to Article
DeBellis  MDChrousos  GPDorn  LDBurke  LHelmers  KKling  MATrickett  PKPutnam  FW Hypothalamic-pituitary-adrenal axis dysregulation in sexually abused girls. J Clin Endocrinol Metab. 1994;78249- 255
Frasier  SDRallison  ML Growth retardation and emotional deprivation: relative resistance to treatment with human growth hormone. J Pediatr. 1972;80603- 609
Link to Article
Anisman  HZaharia  MDMeaney  MJMerali  Z Do early-life events permanently alter behavioral and hormonal responses to stressors? Int J Dev Neurosci. 1998;16149- 164
Link to Article
Van Oers  HJJde Kloet  ERLevine  S Early vs. late maternal deprivation differentially alters the endocrine and hypothalamic responses to stress. Brain Res Dev Brain Res. 1998;111245- 252
Link to Article
Rosenblum  LACoplan  JDFriedman  SBassoff  TGorman  JMAndrews  MW Adverse early experiences affect noradrenergic and serotonergic functioning in adult primates. Biol Psychiatry. 1994;35221- 227
Link to Article
Laudenslager  MLBoccia  MLBerger  CLGennaro-Ruggles  MMMcFerran  BReite  ML Total cortisol, free cortisol, and growth hormone associated with brief social separation experiences in young macaques. Dev Psychobiol. 1995;28199- 211
Link to Article
Kuhn  CMPauk  JSchanberg  SM Endocrine responses to mother-infant separation in developing rats. Dev Psychobiol. 1990;23395- 410
Link to Article
Coplan  JDTrost  RCOwens  MJCooper  TBGorman  JMNemeroff  CBRosenblum  LA Cerebrospinal fluid concentrations of somatostatin and biogenic amines in grown primates reared by mothers exposed to manipulated foraging conditions. Arch Gen Psychiatry. 1998;55473- 477
Link to Article
Pauk  JKuhn  CMField  TMSchanberg  SM Positive effects of tactile vs. kinesthetic or vestibular stimulation on neuroendocrine and ODC activity in maternally deprived rat pups. Life Sci. 1986;392081- 2087
Link to Article
Field  TMSchanberg  SMScafidi  FBauer  CRVega-Lahr  NGracia  RNystrom  JKuhn  CM Effects of tactile/kinesthetic stimulation in pre-term neonates. Pediatrics. 1986;77654- 658
Suomi  SJSeaman  SFLewis  JK Effects of imipramine treatment of separation-induced social disorder in rhesus monkeys. Arch Gen Psychiatry. 1978;35321- 325
Link to Article
Ladd  COOwens  MJNemeroff  CB Persistent changes in corticotropin-releasing factor neuronal systems induced by maternal deprivation. Endocrinology. 1996;1371212- 1218
Higley  JDThompson  WWChampoux  MGoldman  DHasert  MFKraemer  GWScanlan  JMSuomi  SJLinnoila  M Paternal and maternal genetic and environmental contributions to cerebrospinal fluid monamine metabolites in rhesus monkeys (Macaca mullatta). Arch Gen Psychiatry. 1993;50615- 623
Link to Article
Benkelfat  CEllenbogen  MADean  PPalmour  RMYoung  SN Mood-lowering effect of tryptophan depletion: enhanced susceptibility of young men at genetic risk for major affective disorders. Arch Gen Psychiatry. 1994;51687- 697
Link to Article
Sedvall  GFyro  BGullberg  BNyback  HWiesel  FAWode-Helgodt  B Relationships in healthy volunteers between concentrations of monoamine metabolites in cerebrospinal fluid and family history of psychiatric morbidity. Br J Psychiatry. 1980;136366- 374
Link to Article
Rosenthal  NEDavenport  YCowdry  RWWebster  MHGoodwin  FK Monoamine metabolites in cerebrospinal fluid of depressive subtypes. Psychiatry Res. 1980;2113- 119
Link to Article
Lauer  CJSchreiber  WHolsboer  FKrieg  JC In quest of identifying vulnerability markers for psychiatric disorders by all-night polysomnography. Arch Gen Psychiatry. 1995;52145- 153
Link to Article
Rao  UDahl  RERyan  NDBirmaher  BWilliamson  DERao  RKaufman  JNelson  B The relationship between longitudinal clinical course and sleep and cortisol changes in adolescent depression. Biol Psychiatry. 1996;40474- 484
Link to Article
Franz  BKupfer  DJMiewald  JMJarrett  DBGrochocinski  VJ Growth hormone secretion timing in depression: clinical outcome comparisons. Biol Psychiatry. 1995;38720- 729
Link to Article
Thase  MEKupfer  DJBuysse  DJFrank  ESimons  ADMcEachran  ABRashid  KFGrochocinski  VJ Electroencephalographic sleep profiles in single-episode and recurrent unipolar forms of major depression, I: comparison during acute depressive states. Biol Psychiatry. 1995;38506- 515
Link to Article

Correspondence

CME
Meets CME requirements for:
Browse CME for all U.S. States
Accreditation Information
The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
Note: You must get at least of the answers correct to pass this quiz.
You have not filled in all the answers to complete this quiz
The following questions were not answered:
Sorry, you have unsuccessfully completed this CME quiz with a score of
The following questions were not answered correctly:
Commitment to Change (optional):
Indicate what change(s) you will implement in your practice, if any, based on this CME course.
Your quiz results:
The filled radio buttons indicate your responses. The preferred responses are highlighted
For CME Course: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes
Indicate what changes(s) you will implement in your practice, if any, based on this CME course.
Submit a Comment

Multimedia

Some tools below are only available to our subscribers or users with an online account.

Web of Science® Times Cited: 54

Related Content

Customize your page view by dragging & repositioning the boxes below.

Articles Related By Topic
Related Collections