Neuropsychological functioning in girls with premature adrenarche.

Contemporary research indicates that brain development occurs during childhood and into early adulthood, particularly in certain regions. A critical question is whether premature or atypical hormone exposures impact brain development (e.g., structure) or function (e.g., neuropsychological functioning). The current study enrolled 40 girls (aged 6-8 years) diagnosed with premature adrenarche (PA) and a comparison group of 36 girls with on-time maturation. It was hypothesized that girls with PA would demonstrate lower IQ and performance on several neuropsychological tasks. The potential for a sexually dimorphic neuropsychological profile in PA was also explored. No significant univariate or multivariate group differences emerged for any neuropsychological instrument. However, effect size confidence intervals contained medium-sized group differences at the subscale level. On-time girls performed better on verbal, working memory, and visuospatial tasks. Girls with PA showed improved attention, but not a sexually dimorphic profile. These results, though preliminary, suggest that premature maturation may influence neuropsychological functioning.

Growth hormone secretion in children and adolescents at high risk for major depressive disorder.

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.

Diurnal rhythm of plasma delta-sleep-inducing peptide in humans: evidence for positive correlation with body temperature and negative correlation with rapid eye movement and slow wave sleep.

Since delta-sleep-inducing peptide (DSIP) was isolated in 1977, numerous reports have suggested that this nonapeptide stimulates delta-sleep [slow wave sleep (SWS)]. Although DSIP-like immunoreactivity (DSIP-LI) has been found in the serum of many animals and man, its diurnal rhythm and relation to sleep stages have not been well defined. We hypothesized that circulating levels of this putative sleep hormone would be highest at night and would probably be elevated before or during episodes of SWS. We, therefore, measured plasma DSIP-LI levels every 30 min for 24 h in 12 normal volunteers in whom we obtained simultaneous polygraphic recordings. We found a distinct diurnal rhythm for plasma DSIP-LI levels, with the maximum at 1500 h and the minimum at 0100 h. DSIP-LI levels were substantially lower in rapid eye movement sleep (P < 0.005) and somewhat lower in SWS (P < 0.05) compared to awake values. DSIP-LI levels did not rise before, during, or after a significant percentage of episodes of SWS. We found, however, that the diurnal rhythm of DSIP-LI closely followed that of body temperature with a high degree of correlation (r2 = 0.66; P < 0.0001). We conclude that endogenous elevations of circulating DSIP may be associated with suppression of slow wave and rapid eye movement sleep, and that the circadian rhythm of this peptide is coupled directly or indirectly to that of body temperature.

Hypothalamic-pituitary-adrenal axis dysregulation in sexually abused girls.

Childhood sexual abuse is associated with an increased incidence of age-concurrent and adult psychopathology. Little is known, however, about the biological manifestations and sequelae of childhood sexual abuse. In this study, we characterized the hypothalamic-pituitary-adrenal axis of a self-selected sample of sexually abused and control girls recruited from a prospective longitudinal study. Plasma ACTH and total and free cortisol responses to ovine CRH (oCRH) stimulation were measured in 13 sexually abused and 13 control girls, aged 7-15 yr. Psychiatric profiles and 24-h urinary free cortisol (UFC) measures were also obtained. Sexually abused girls had a greater incidence of suicidal ideation (chi 2 = 4.51; df = 1; P < 0.05), suicide attempts (chi 2 = 4.51; df = 1; P < 0.05), and dysthymia (chi 2 = 8.85; df = 1; P < 0.01) than control girls. Sexually abused girls showed significantly lower basal (t = 2.1; df = 24; P < 0.05), and net oCRH stimulated (t = 2.2; df = 24; P < 0.05) ACTH levels and significantly reduced total ACTH responses (t = 2.5; df = 24; P < 0.05) compared with control subjects. Their total and free basal and oCRH-stimulated plasma cortisol levels and 24-h UFC measures, however, were similar to those in controls. The attenuated plasma ACTH with corresponding robust plasma cortisol responses to oCRH stimulation and normal 24-h UFC measures in sexually abused girls suggest a dysregulatory disorder of the HPA axis in these individuals. This may reflect pituitary hyporesponsiveness to oCRH. The ability of sexually abused subjects to correct for the proposed pituitary hyporesponsiveness to CRH may be related to their young age and the presence of intact glucocorticoid feedback regulatory mechanisms.

The longitudinal course of psychopathology in Cushing's syndrome after correction of hypercortisolism.

Endogenous Cushing's syndrome (CS) is associated with significant psychopathology during the course of the disease. The purpose of this study was to evaluate the psychological and endocrine status of patients with CS after correction of their hypercortisolism. Thirty-three patients with active CS were examined before and at 3 months (28 patients), 6 months (25 patients), and 12 months (29 patients) after correction of hypercortisolism. Before cure, 66.7% of the patients had significant psychopathology, with the predominant diagnosis of atypical depressive disorder (AD) in 51.5% and/or major affective disorder in 12%. After cure, overall psychopathology decreased significantly to 53.6% at 3 months, 36% at 6 months, and 24.1% at 12 months, when there was a parallel recovery of the hypothalamic-pituitary-adrenal axis assessed by serial morning ACTH stimulation tests. There was an inverse correlation between psychological recovery and baseline morning cortisol, but no correlation with ACTH-stimulated cortisol values at 60 min. AD continued to be the prevailing diagnosis after correction of hypercortisolism, whereas the frequency of suicidal ideation and panic increased. The presence of AD before and after correction of hypercortisolism might be due to glucocorticoid-induced suppression of hypothalamic CRH secretion. The slight increase in the incidence of panic after correction of hypercortisolism might be due to a decreased glucocorticoid restraint at the central arousal/sympathetic catecholaminergic system. We conclude that CS is associated with AD symptomatology, which gradually improves with time after correction of hypercortisolism. Health care providers should be aware of changes in symptomatology, including suicidal ideation and panic attacks, that occur in a subgroup of patients.

Serum and saliva cortisol relations in adolescents during pregnancy and the early postpartum period.

The purpose of this investigation was to examine: (1) relations between serum and saliva cortisol in adolescents in pregnancy and early postpartum and (2) short-term consistency of serum and saliva cortisol across three samples, 20 minutes apart, as well as the long-term consistency from pregnancy to early postpartum. Pregnant adolescents (n = 40), ages 14 to 19 years, were enrolled in this study. Subjects were seen at 20 weeks gestation or earlier (T1), 34-36 weeks gestation (T2), and 2-3 weeks postpartum (T3). Blood samples were drawn at T1 and T3, at 0, 20, and 40 minutes. Saliva samples were collected across the same 40-minute period at T1, T2, and T3. Spearman rho (rs) correlation coefficients between serum and saliva ranged from 0.72 to 0.77 (T1), and 0.42 to 0.60 (T3) (p < or = 0.05). Short-term consistency between serum cortisol samples was 0.86-0.97 at T1 and 0.60-0.82 at T3. Short-term consistency for saliva cortisol samples was 0.70-0.96 at T1, 0.91-0.95 at T2, and 0.64-0.89 at T3. Long-term consistency (T1 to T3) for serum and saliva cortisol was low. Individual differences as well as dramatic changes in the endocrine environment in pregnancy and the early postpartum period may explain the more moderate serum-saliva correlations in the postpartum period.

The endocrinology of stress and stress system disorders in adolescence.

The endocrinology of stress and the stress response is reviewed briefly. The interrelations of the stress system with various other endocrine axes and how this system may influence adolescent development and its various disorders are discussed.

Cortisol reactivity and anxiety and depression in pregnant adolescents: a longitudinal perspective.

The purpose of this investigation was to examine: (1) the relations among cortisol reactivity (short term changes in cortisol concentration) and anxiety and depression symptoms in adolescents during pregnancy and early postpartum, and (2) cortisol reactivity and psychosocial variables as predictors of anxiety and depression symptoms in pregnancy and early postpartum. Cortisol reactivity, an index of hypothalamic-pituitary-adrenal activity, was hypothesized to be a vulnerability factor for poor physical and mental health outcomes in adolescents. Forty adolescents aged 14 to 19 years (M = 17.3, SD = 1.3) were enrolled in the study and were seen at < 20 weeks gestation (T1), 34-36 weeks gestation (T2), and 2-3 weeks postpartum (T3). Blood was drawn for cortisol at T1 and T3. Psychological assessments of anxiety and depression symptoms, life optimism, and self-worth were administered at T1, T2, and T3. There were significant correlations among cortisol reactivity and anxiety and depression symptoms at T1 and T3, but the correlations were the reverse of the hypothesized direction. Pregnant adolescents with increased cortisol reactivity (cortisol concentrations that increased across a 40-min period) had fewer symptoms of anxiety and depression than other adolescents. Longitudinal analyses showed that anxiety and depression symptoms at T1 were a stronger predictor of postpartum anxiety and depression than was cortisol reactivity, life optimism, self-worth, or age at pregnancy.

PIP: The authors hypothesized cortisol reactivity to be a vulnerability factor for poor physical and mental health outcomes in adolescents. This paper reports findings from a study of the relations among cortisol reactivity and anxiety and depression symptoms in pregnancy and early postabortion. 40 adolescents aged 14-19 years were enrolled in the study and seen at less than 20 weeks gestation, 34-36 weeks gestation, and 2-3 weeks postpartum. Blood was drawn for cortisol at the 1st and 3rd time indexes. At all times, psychological assessments of anxiety and depression symptoms, life optimism, and self-worth were administered. Significant correlations were found among cortisol reactivity and anxiety and depression symptoms at T1 and T3, but in a direction opposite of that which was hypothesized. Pregnant adolescents with increased cortisol reactivity had fewer symptoms of anxiety and depression than other adolescents. Longitudinal analyses further demonstrated that anxiety and depression symptoms at T1 were stronger predictors of postpartum anxiety and depression than were cortisol reactivity, life optimism, self worth, or age at pregnancy.

Biopsychological and cognitive differences in children with premature vs. on-time adrenarche.

BACKGROUND: Puberty consists of 2 components: gonadarche and adrenarche. Both components have distinct endocrine changes. Adrenarche has virtually been ignored with respect to examining hormone-behavior relations. OBJECTIVES: To provide descriptive biological and behavioral information on children with premature adrenarche (PA) and to examine differences in biological, psychological, and cognitive variables of children with PA and a healthy comparison group of children with on-time adrenarche. DESIGN: Descriptive pilot study. SETTING: A consecutive sample of patients was recruited from pediatric endocrine clinics; comparison children were recruited from the community. PARTICIPANTS: Children aged 6 to 9 years. Mean (+/-SD) age of children with PA (n = 9) was 7.8 (+/-1.3) years; of children with on-time adrenarche (n = 20), 8.0 (+/-1.2) years. METHODS AND MEASURES: Serum and saliva samples were collected for measurement of hormone concentrations. Questionnaires, tests, and interviews were completed by children and parents. RESULTS: Compared with the on-time group, the PA group had significantly higher concentrations of adrenal androgens, estradiol, thyrotropin, and cortisol. By parent report on the Diagnostic Interview Schedule for Children, 4 children (44%) met diagnostic criteria for psychological disorders (primarily anxiety disorders). The PA group also had more self-reported depression and parent-reported behavior problems and lower scores on various intelligence tests. CONCLUSIONS: Although PA is considered a normal variation of pubertal development that warrants no medical intervention, PA presents with significant psychosocial problems. Children with PA may need psychological evaluation and follow-up. Future studies should confirm these findings with a larger sample and examine the long-term ramifications of this early presenting abnormality.

Baseline thyroid hormones in depressed and non-depressed pre- and early-pubertal boys and girls.

OBJECTIVE: To examine baseline thyroid hormones in a large group of well-characterized pre- and early-pubertal boys and girls who met criteria for major depressive disorder (MDD) and a comparison group of normal children without psychiatric disorders. METHODS: 45 children with MDD (10.6 years +/- 1.4 year) and 56 healthy controls (10.0 +/- 1.7 year) who participated in a large, psychobiologic protocol are included in this report. As part of the screening for eligibility, baseline samples were drawn for thyroxine (T4), triiodothyronine (T3) uptake, and thyroid stimulating hormone (TSH). Free thyroxine index (FTI) also was computed. RESULTS: Between-group analyses were carried out controlling for various demographic variables significantly related to thyroid hormones [e.g. age, gender, body mass index (BMI) and their interactions]. For many hormones there were significant effects for age and gender. For T4, MDD boys had lower T4 compared with boys in the normal group. No differences were noted between MDD girls and normal girls. For TSH, MDD boys had lower concentrations compared with normal boys while no differences were noted in girls. For T3 uptake, the MDD group had lower uptake compared with the normal group. For FTI, there were no group differences. Similar to most studies of adults with depression, all our subjects were euthyroid. Unlike the adult studies, we found lower T4 concentrations in the MDD group rather than higher. Group differences in thyroid hormones were noted primarily in boys. The large sample size of this study allowed for the control of multiple variables, which has not been done in past studies. Without such controls, true findings may be masked in other studies of depression. Thus, our findings suggest the possibility of developmental differences in the relation of thyroid hormone and depression.

Response to oCRH in depressed and nondepressed adolescents: does gender make a difference?

OBJECTIVE: To examine the hypothesis that hypothalamic-pituitary-adrenal responses to stress vary across gender, contributing to gender differences in the prevalence of depression. METHOD: This study examined gender differences between depressed (n = 21) and control (n = 20) adolescents in adrenocorticotropic hormone (ACTH) and cortisol response to two ovine corticotropin-releasing hormone (oCRH) tests, at baseline and following a cognitive stressor. RESULTS: Boys had higher (p < .05) measures of ACTH than girls, regardless of depression status, whereas corresponding cortisol parameters were similar in both groups. Cortisol measures were higher (p < .05) at time 1 than at time 2 in both groups, a phenomenon that might reflect the novelty of the situation. CONCLUSIONS: Gender differences in hormone responses may be related to differences in peripheral metabolism of ACTH, resulting in changes of immunoreactivity but not bioactivity or a different set point of the hypothalamic-pituitary-adrenal axis. The pattern of ACTH and cortisol responses to oCRH and the 24-hour excretion of free cortisol was normal in adolescents with depression, probably reflecting normal negative feedback mechanisms at this age or that most of these patients suffer from atypical rather than melancholic depression.

Thyroid hormone concentrations in depressed and nondepressed adolescents: group differences and behavioral relations.

OBJECTIVE: To examine thyroid hormone concentrations and the influence of these hormones on mood and problem behaviors in adolescents with depression. METHOD: The sample included 21 depressed adolescents and 20 matched control adolescents. Blood was drawn to measure thyroid-stimulating hormone (TSH), free thyroxine (FT4), thyroxine (T4), and triiodothyronine (T3). Major depression (MD), attention deficit (AD), and obsessive-compulsive (OC) symptom scores were abstracted from the Diagnostic Interview Schedule for Children. Total behavior problem scores from the Youth Self-Report also were obtained. RESULTS: Paired analysis revealed there were no significant group or gender differences or group by gender interactions for TSH, T4, or T3. For FT4, however, there were significant group differences (p = .008) showing lower concentrations in depressed adolescents than control subjects, suggesting that the former might be functionally hypothyroid. Although there were no significant correlations of TSH with any of the psychological measures obtained, in the depressed group correlations were negative (although not always significant) with FT4 and total behavior problems (r = -.40, p = .09), as well as with symptom scores of MD (r = -.25, p = .288), OC (r = -.56, p = .011), and AD behaviors (r = -.57, p = .008). Higher numbers of symptom scores of OC and AD were related to lower concentrations of FT4. CONCLUSIONS: FT4 concentrations were lower in depressed adolescents. These findings suggest a relationship between negative behaviors and dysfunction of the hypothalamic-pituitary-thyroid axis in adolescents with depression.

Hormonal and behavioral homeostasis in boys at risk for substance abuse.

This study modeled the influences of cortisol reactivity, androgens, age-corrected pubertal status, parental personality, family and peer dysfunction on behavioral self-regulation (BSR), in boys at high (HAR) and low average risk (LAR) for substance abuse. Differences between risk groups in cortisol and androgen concentrations, and cortisol reactivity were also examined. Subjects were 10- through 12-year-old sons of substance abusing fathers (HAR; n = 150) and normal controls (LAR; n = 147). A multidimensional construct of BSR was developed which utilized multiple measures and multiple informants. Boys reported on family dysfunction and deviant behavior among their peers. Parents reported on their propensity to physically abuse their sons, and their own number of DSM-III-R Antisocial Personality Disorder symptoms. Endocrine measures included plasma testosterone, dihydrotestosterone, and salivary cortisol. HAR boys, compared to LAR boys, had lower mean concentrations for testosterone, dihydrotestosterone, salivary cortisol prior to evoked related potential testing, and lower cortisol reactivity. The number of maternal Antisocial Personality Disorder symptoms, parental potential for physical abuse, degree of family dysfunction, and peer delinquency were significantly associated with BSR. Parental aggression antisocial personality symptoms and parental physical abuse potential are likely to influence sons' behavioral dysregulation and homeostatic stress reactivity. These key components of liability are posited to increase the likelihood of developing suprathreshold Psychoactive Substance Use Disorder (PSUD).

Informed consent in children and adolescents: age, maturation and psychological state.

PURPOSE: The purpose of this investigation was to examine the relationship of understanding of research participation to anxiety, control, and stage of cognitive development. METHODS: Participants included 44 boys and girls ages 7 to 20 years. All were inpatients for the first time in pediatric units of a research hospital. Twenty participants were admitted for experimental treatment of pediatric cancers and 24 were admitted for a 3-week treatment of extreme obesity. An interview was conducted to assess 12 elements of knowledge of research participation of a medical protocol. The interview was coded for: 1) knowledge of research participation score, 2) weighted knowledge of participation in research score (based on physician ratings of what was most-to-least important for children and adolescents to know), and 3) global control (perceived control over life, illness and treatment). A measure of anxiety and one Piagetian task to measure stage of cognitive development also were administered. RESULTS: Pearson correlations, significant at p < or = .05, were as follows: knowledge of participation in research and global control, (r = .40) and weighted knowledge of participation in research score and global control (r = .38). Hierarchical regression showed that the best predictors of knowledge of research participation or the weighted knowledge of research participation score was global control alone or an interaction of global control with anxiety. CONCLUSIONS: Emotional factors were more frequently related to understanding of research participation than age or cognitive development. Providing medical environments that decrease anxiety and increase control may enhance children's and adolescent's understanding of the research process.

Reasoning about illness in ill and healthy children and adolescents: cognitive and emotional developmental aspects.

Anxiety level, perception of control over illness, stage of cognitive development, and stage of reasoning about illness were examined in pediatric oncology, obese, and healthy children and adolescents. Among the groups, there were no mean differences with regard to any of these measures. Older participants in the higher stages of cognitive development were higher on stage of reasoning about illness in general and their own illness than were younger and less cognitively mature participants. In the pediatric oncology and obese groups, participants higher on perception of control over illness were higher on stage of reasoning about illness in general and their own illness, in particular, than those lower on perception of control. Anxiety level was not related to stage of reasoning about illness, but participants higher on anxiety were lower on perception of control over illness. Clinical implications of the findings are discussed.

Critical periods of neuroendocrine development: effects of prenatal xenobiotics.

Phenobarbital, when administered prenatally in a small dose to animals, produced profound, and permanent effects on reproductive function in the offspring. Preliminary analysis of a unique cohort of adolescents who were exposed to phenobarbital in utero, suggests that long-term effects are also evident in the human. The precise nature of these effects is currently being determined and will be reported separately. These effects may be qualitatively and quantitatively different from effects seen in animals because of species difference in the timing or neuroendocrine differentiation. Of greater importance, however, is the fact that biologic and pharmacologic effects can be seen in the human following exposure to xenobiotics perinatally. Implications for other pharmacologic agents await further investigation. The rat model appears to have validity for extrapolation to man.

Physiological and behavioral aspects of stress in adolescence.

Gonadal and adrenal hormone levels appear to be linked to the stressors experienced by young adolescents. Adjustment problems were accompanied by a profile of lower gonadal steroids and higher adrenal androgen levels, primarily androstenedione. Later gonadal maturation may be a result of stress suppressing the reproductive axis. Higher levels of androstenedione may be indicative of chronic levels of stress. However, the findings for androstenedione are complicated by the fact that androstenedione was related to cortisol only in males. Furthermore, androstenedione as a weak androgenic has low potential for affecting behavior, directly. Cortisol levels were related to the frequency of distress behavior in a challenging situation. The relations disappeared with experience in the setting. These findings are consistent with prior animal and human studies. However, while distress behavior in a challenging situation decreased over the one-year period, cortisol levels did not. Sustained physiological arousal in a challenging situation may have long-term implications for the mental health of adolescents. A question for further exploration is whether individual differences in reactivity in one challenging situation, like the clinic visit, is predictive of reactivity in other settings. Adolescence appears to be an ideal period of development in which to examine the interactions between environmental and physiological causes and sequelae of stress. It is characterized by measurable changes in hormonal status and physical maturation and behavior. Studying the intricate interactions between these two sets of changes has only just begun. A larger question yet to be examined is whether interaction between hormones and behavior are unique to adolescence or whether they are indicative of hormone-behavior processes characteristic of the entire life-span. Adjustment and social stressors, adrenal activation, and reproductive maturation may constitute a "vicious" cycle of interrelated factors during adolescence. Adjustment problems could cause activation of the adrenal glands which would cause gonadal suppression and later maturation. The latter could constitute an added stressor reentering the cycle and potentiating the "abnormality". In our population of normal adolescents, this cycle is obviously active within a normal range. In these adolescents stress arising from either endogenous or exogenous sources was not a debilitating force. Rather, they fell within a normal range with various degrees of adjustment, adrenal activation and gonadal maturation.(ABSTRACT TRUNCATED AT 400 WORDS)

Cognitive function in patients with Cushing syndrome: a longitudinal perspective.

The purposes of this study were to examine the level of improvement of cognitive function 12 months posttreatment in adult patients with Cushing syndrome (CS), the relationships of cognitive function to duration of CS or recovery of the hypothalamic pituitary adrenal (HPA) axis, and depression and improved cognitive functioning. Thirty-three patients with CS and a matched comparison group were enrolled. IQ, depression, and endocrine factors were measured during the active phase of CS and at 12 months posttreatment for CS. Results show no group differences in cognitive function across time but a trend for CS patients to have lower IQ scores at baseline. Individual differences in performance were striking. For some subscales of IQ there was a positive relationship with recovery of the HPA axis and a negative relationship with duration of CS as well as an improvement if depression had decreased. Limitations of the study are cited along with clinical implications and directions for future research.

Adolescents' agreement to test for HIV when different testing methods are offered.

Offering rapid HIV testing improves rates of testing in adults, but little is known about whether offering adolescents a choice of testing methods increases rates of testing. The aims of the study were to determine rates of HIV testing in adolescents when different testing methods were offered and explore factors associated with agreement to be tested for HIV. Participants (n= 200, sexually experienced 13-22 year olds) were recruited from an urban adolescent clinic, completed a 99-item theory-based survey and were offered their choice of venipuncture, rapid fingerstick or rapid oral fluid HIV testing. Approximately half (49.5%) agreed to HIV testing. Male gender, parental completion of high school, intention to test for HIV if offered by clinician and higher perceived likelihood of current HIV infection were independently associated with agreement to test. Combining new strategies, such as opt-out testing, with routine testing may be needed to improve rates of adolescent HIV testing.