Corticotropin releasing hormone increases apparent potency of adrenocorticotropic hormone stimulation of cortisol secretion.

HYPOTHESIS: Corticotropin releasing hormone (CRH) has a regulatory effect on cortisol secretion in addition to its classic effect of stimulating adrenocorticotropic hormone (ACTH) secretion. REVIEW: There is growing evidence of "long-loop" and paracrine adrenal stimulation by CRH. Data from a study of the ovine-corticotropin releasing hormone (oCRH) stimulation test in 13 sexually abused girls and 13 normal controls was used in Montecarlo simulations of the hypothalamic-pituitary-adrenal axis, to get estimates of adrenal sensitivity to ACTH and cortisol elimination kinetics before and after oCRH administration. In both controls and sexually abused girls, ACTH had an apparent greater effect on cortisol secretion after administration of oCRH compared to its effect during the baseline period. This lends support to the hypothesis and suggests that it should be tested experimentally.

Zora: a pilot virtual community in the pediatric dialysis unit.

We describe a five-month pilot project conducted in the dialysis unit at Boston's Children's Hospital. Pediatric patients with renal disease used the Zora therapeutic community program while undergoing hemodialysis. Zora is a 3D multi-user computer environment designed at the MIT Media Laboratory to help young people explore issues of identity, while engaging in a virtual community. Users build "virtual rooms" and populate them with objects and characters, program them with storytelling behaviors, and converse with other young people in real-time through a virtual character representing themselves. It was specifically designed to help young people explore issues of identity, while engaging in a participatory virtual community. This paper presents the experience and evaluates the feasibility and safety of using Zora in a hospital setting. It describes how Zora facilitated explorations of identity and mutual patient support and interaction. Finally it also presents design recommendations for future interventions of this kind. More generally, this paper explores the potential of technology specifically designed with therapeutic purposes to help patients cope with their illness.

A prospective open-label treatment trial of olanzapine monotherapy in children and adolescents with bipolar disorder.

OBJECTIVE: The goal of this study was to assess the effectiveness and tolerability of olanzapine in the treatment of acute mania in children and adolescents. METHODS: This was an 8-week, open-label, prospective study of olanzapine monotherapy (dose range 2.5-20 mg/day) involving 23 bipolar youths (manic, mixed, or hypomanic; 5-14 years old). Weekly assessments were made using the Young Mania Rating Scale (YMRS), Clinical Global Impressions Severity Scale (CGI-S), Brief Psychiatric Rating Scale, and Children's Depression Rating Scale. Adverse events were assessed through self-reports, vital sign and weight monitoring, laboratory analytes, and extrapyramidal symptom rating scales (Barnes Akathisia Scale, Simpson-Angus Scale, and Abnormal Involuntary Movement Scale). RESULTS: Twenty-two of the 23 youths (96%) completed the study. Olanzapine treatment was associated with significant improvement in mean YMRS score (-19.0 +/- 9.2, p < 0.001). Using predefined criteria for improvement of > or = 30% decline in the YMRS and a CGI-S Mania score of < or = 3 at endpoint, the overall response rate was 61%. Overall, olanzapine was well tolerated, and extrapyramidal symptom measures were not significantly different from baseline. Body weight increased significantly over the study (5.0 +/- 2.3 kg, p < 0.001). CONCLUSIONS: Open-label olanzapine treatment was efficacious and well tolerated in the treatment of acute mania in youths with bipolar disorder. Future placebo-controlled, double-blind studies are warranted.

Illness-related concerns of mothers of children with congenital heart disease.

OBJECTIVE: This study examined concerns expressed by mothers of children with congenital heart disease (CHD). The relationships among mothers' concerns, medical severity, and mother's emotional state were examined at two points in time. METHOD: Thirty-eight mothers of children with CHD aged 3 to 16 completed semistructured interviews and rating scales during hospitalization and 2 to 4 weeks after discharge. Mothers rated their distress about illness-related concerns, as well as their own depressed mood and anxiety. Mothers and two cardiologists rated the medical severity of each child's disease. RESULTS: Mothers' concerns were reliably grouped into five categories: medical prognosis, quality of life, psychosocial functioning, effects on family, and financial issues. During hospitalization, mothers were most concerned about medical prognosis. Distress about most concerns decreased postdischarge, as did mother's anxiety and depressed mood. Mothers' perceptions of medical severity were associated with distress about psychosocial issues postdischarge. Mother's anxiety was not associated with number of concerns reported, or with distress about those concerns. Maternal depressed mood was associated with fewer illness-related concerns, but greater distress about those concerns. CONCLUSIONS: Illness-related concerns can be meaningfully categorized and are not necessarily a function of disease severity or mother's emotional state. An awareness of common concerns will improve clinical care by enabling practitioners to anticipate and address concerns in a proactive way. The results may inform the development of supportive mental health interventions for families of children with CHD.

Implementation of an electronic medical record system in a pediatric psychopharmacology program.

The design, implementation, and utilization of an electronic medical record system (EMRS) in a pediatric psychopharmacology clinic is described. The EMRS is a relational database with information entered directly by the clinician during a patient visit. It has been used during more than 2590 patient visits with 805 patients. Complete clinical documentation and simultaneous data entry as well as computer generated prescriptions for the patient were accomplished 75% of the time within a 20-min medication management session. One hundred consecutive parents of patients were asked to fill out a five-question survey to begin to assess the impact of the application. Of the 87 parents who responded, all (100%) noted that the doctor paid attention to their concerns. Between 88 and 90% of the parents reported that the use of the computer is a 'good' thing, made it easier to work with the doctor, and that they understood why the computer was being used. The findings support that the development and implementation of an EMRS with direct clinician information entry within pediatric psychopharmacology clinic, is feasible.

The experience journal: a computer-based intervention for families facing congenital heart disease.

OBJECTIVE: To test the feasibility and safety of a computer-based application designed to facilitate the healthy coping of children and their families who must contend with significant congenital heart disease (CHD). The application, called the Experience Journal (EJ), is a psychoeducational intervention based on a narrative model involving the sharing of personal stories about an illness. METHOD: Testing was conducted in 2 phases. In phase 1, 9 parents of children with CHD and 1 adult with CHD were asked to use the EJ. After utilization, semistructured interviews assessed EJ usability and safety. In phase 2, 40 mothers of children with CHD used the EJ during a hospitalization. Assessment of feasibility and safety was measured through the use of semistructured interviews prior to EJ utilization and 2 to 4 weeks after hospital discharge. RESULTS: Results revealed that the EJ was safe and useful for decreasing social isolation, increasing understanding of familial feelings about cardiac illness, and fostering positive reactions in mothers. CONCLUSIONS: Computer-based interventions that present psychoeducational and medical information closely connected to "one's own story" may open up new possibilities for families facing pediatric illnesses.

Epilepsy in children and adolescents.

Epilepsy is common in the pediatric population and can significantly affect the health and quality of life of the child and family. There are many causes of childhood seizures and many forms of treatment, including pharmacologic and surgical modalities. Psychiatric disease occurs with higher incidence in children with epilepsy, and psychiatric disease in children also must be differentiated from epilepsy. Many medications are used to treat epilepsy and psychiatric disease, all of which interact with each other pharmacodynamically, as well as acting on the clinical manifestations of the disorders. These factors, and the complicated interface between epilepsy and psychiatry, must be considered in the successful management of children with epilepsy.

Using 'off the shelf', computer programs to mine additional insights from published data: diurnal variation in potency of ACTH stimulation of cortisol secretion revealed.

We describe the use of available computer programs to mine additional insights from published data. Graphs from four studies of ACTH and cortisol plasma levels collected throughout the 24 h day in humans were scanned into digital form and the data points extracted. To investigate the magnitude of ACTH stimulation of cortisol secretion across the 24 h, Monte Carlo methods were used to fit the parameters of a computer model of the ACTH-adrenal axis to the extracted data. ACTH was found to have a greater effect on cortisol secretion during the peaks of the cycle than at the nadir. This finding could not be explained by previously published dose response curves of ACTH effect. This implies that other modulators influence the effect of ACTH on the adrenal. This study also demonstrates how available computer programs can be used to examine models of physiologic regulation using data already available in the literature.

Experience journals: using computers to share personal stories about illness and medical intervention.

Medical advances make it increasingly possible for children with previously fatal illness to live and thrive. However, a significant number still experience repeated operations, hospitalization, and invasive procedures, or need special care at home. Many do so with little or no intervention to help them and their families cope with the emotional stresses involved. One significant source of emotional and cognitive support is the community of patients and families who have experienced similar medical procedures. However, in spite of a general willingness to share experiences, communication among patients and families is usually limited. To facilitate this process, we are investigating the use of computer technology to record, organize, and display stories about the experiences of families with children who have been treated for cardiac and neurological illness at Children's Hospital, Boston. We are asking children and their families to record text and multimedia vignettes describing some aspect of their illness, coping strategies, or care that might be useful to others. These contributions will be available for browsing at a secure World-Wide-Web site. However, economic realities preclude reliance on a professional site administrator to organize and monitor what we hope to be a rapidly growing Web site with a large, distributed authorship. The need to make the Web site fully accessible to users who have varying familiarity with computers and Web browsing imposes further constraints. We are therefore developing software to automate the process of managing and organizing an easily accessed Web site that contains an "Experience Journal." We describe this software, the rationale for its development, and our plans for its use in the coming year.

A computer simulation of the hypothalamic-pituitary-adrenal axis.

This paper describes the construction of a computer model that simulates the hypothalamic-pituitary-adrenal axis (HPA axis) regulation of cortisol production. It is presented to illustrate the process of physiological modeling using standard "off the shelf" technologies. The model simulates components of the HPA axis involved in the continuous secretion and elimination of cortisol, adrenocorticotropin (ACTH), and corticotropin releasing hormone (CRH). The physiological relations of these component pieces were modeled based on the current knowledge of their functioning. Rate constants, half lives, and receptor affinities were assigned values derived from the experimental literature. At its current level of development the model is able to accurately simulate the timing, magnitude and decay of the ACTH and cortisol concentration peaks resulting from the ovine-CRH stimulation test in normal and hypercortisolemic patients. The model will be used to predict the effects of lesions in different components of the HPA axis on the time course of cortisol and ACTH levels. We plan to use the model to explore the experimental conditions required to distinguish mechanisms underlying various disorders of the HPA axis, particularly depression. Efforts are currently underway to validate the model for a large variety of normal and pathological perturbations of the HPA axis.

Using neural networks to model personality development.

A neural network approach to modeling the development of personality traits through social learning is presented. From the more general model the special case of a network mapping four situation dimensions (input neurons) into seven dimensional personality traits (output neurons) is described. This network is allowed to learn with input/output sets representing conditions suspected of leading to a borderline personality disorder. The network's ability to learn these pattern pairs is demonstrated. The trained network is then presented with new input (situational) patterns and is shown to respond to these new situations with output patterns consistent with a borderline personality disorder. The neural network model is thus shown to have important advantages over other personality models in that it can predict what situations will produce shifts in personality traits, for example from active to passive. This model provides a quantitative and reproducible framework within which to discover and test theories of personality development. It is hoped that it will extend our ability to predict human behavior.

Testing the psychogenic vomiting diagnosis. Four pediatric patients.

We treated four patients with chronic vomiting during childhood in whom a tentative diagnosis of psychogenic vomiting was made after an extensive evaluation. In each case, the diagnosis was reconsidered during the course of treatment, as observations about the patients and their response to interventions accumulated. In three instances, these observations did not fit those expected if the diagnosis of psychogenic vomiting was correct. This led to a reexamination of the organic evaluation and the discovery of an undiagnosed organic contribution to the vomiting. In the fourth patient, gastric emptying studies confirmed that there was a strong psychological contribution to the vomiting, and helped to more carefully define this contribution. Family and individual psychotherapy and treatment were aided by the greater clarity in diagnosis.

Postsynaptic localization of 5-HT1D receptor binding sites in human caudate.

5-hydroxytryptamine1D (5-HT1D) receptor binding sites were quantified by saturation studies in the postmortem caudate nucleus and frontal cortex of individuals with Huntington's disease and control individuals with no known neurological disease. 3H-5-HT was used as the radioligand in the presence of 100 nM 8-OH-DPAT and 100 nM mesulergine in order to restrict radioligand binding to 5-HT1D receptors. No alteration in KD value was detected in Huntington's disease as compared to control brain tissue. However, the density (Bmax) of the 5-HT1D site was significantly decreased (P less than 0.01) in the caudate, but not the frontal cortex, of Huntington's disease versus control individuals. By contrast, no significant difference was found in Bmax or KD of [3H]paroxetine binding between control and Huntington's caudates. These data suggest that a significant number of caudate 5-HT1D receptors are located on the intrinsic neurons of the striatum as opposed to 5-HT nerve terminals.

Serotonin receptor and reuptake sites: pharmacologic significance.

The past decade has seen important advances in the clinical use of serotonergic agents. The authors summarize the current status of selective agents for 5-HT receptor subtypes and their utility in the treatment of human neuropsychiatric disorders. The putative novel anxiolytic effects of 5-HT1A partial agonists such as buspirone, the unique and potent antiemetic effects of 5-HT3 antagonists in cancer chemotherapy, and the antidepressant effects of selective 5-HT uptake blockers such as fluoxetine are excellent examples of the clinical relevance of selective 5-HT receptor agents. The increasing ability to modulate serotonergic neurotransmission via distinct serotonin (5-HT) receptor subtypes should greatly facilitate the analysis of the role of 5-HT in both normal and abnormal human brain function.