Biomedical subjects
Publications and source records attributed to L D Dorn.
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.
We examined the capacity of children, adolescents, and young adults to assent and consent to participation in biomedical research, and what physician-investigators believe is important for patients in these age groups to know about such participation. The sample included 44 male and female subjects, ranging in age from 7 to 20 years, who were hospitalized to treat either pediatric cancer or obesity. The participants completed a structured interview that assessed knowledge of research participation using the elements outlined in the federal guidelines for informed consent. The study subjects were most knowledgeable about those elements of consent that assessed concrete information (e.g., freedom to ask questions, time elements involved, and the benefits of participation). They were less knowledgeable about those elements of informed consent that assessed abstract information (e.g., scientific vs therapeutic purpose of the study, and alternative treatments). Chronologic age was not related to knowledge of the elements of informed consent. The strategies that the study subjects used to reason about participation in research appeared to parallel their reasoning about other physical phenomena.
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.
Phenobarbital, when administered prenatally to animals, produced profound and prominent effects on reproduction. Preliminary analysis of a unique cohort of adolescents who were exposed to phenobarbital in utero suggests that long-term effects may be evident in the human as well.
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)
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Cross-sectional data are presented on 108 young adolescents (56 boys, 52 girls), ages 9 to 14 years. The measures were: for all subjects, pubertal stage (Tanner criteria for genital/breast and pubic hair stage); height and weight; serum hormone concentrations for gonadotropins (luteinizing hormone and follicle-stimulating hormone), sex steroids (testosterone, estradiol, and the computed testosterone to estradiol ratio), adrenal androgens (dehydroepiandrosterone, dehydroepiandrosterone sulfate, and androstenedione), and testosterone-estradiol binding globulin. In addition, testicular volume for boys and menarchial status for girls are reported. The study goal was to provide interrelations among these measures, based on the same sample, and examine their interchangeability. Results suggest that it would be reasonable to compare research across as well as within studies based on different markers. Multiple regression analysis showed that the strongest hormone correlates of pubertal development were androgen levels (primarily testosterone in boys and primarily dehydroepiandrosterone sulphate and androstenedione in girls). Estradiol level in girls was the strongest correlate only for menarchial status. Level of testosterone-estradiol binding globulin, which was lower at successive pubertal stages for boys and showed no consistent differences for girls, may be a useful measure for studying the developmental processes and gender differences during puberty.
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.
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.
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