Pharmacogenetics: ethical issues and policy options

Pharmacogenetics offers the prospect of an era of safer and more effective drugs, as well as more individualized use of drug therapies. Before the benefits of pharmacogenetics can be realized, the ethical issues that arise in research and clinical application of pharmacogenetic technologies must be addressed. The ethical issues raised by pharmacogenetics can be addressed under six headings: (1) regulatory oversight, (2) confidentiality and privacy, (3) informed consent, (4) availability of drugs, (5) access, and (6) clinicians' changing responsibilities in the era of pharmacogenetic medicine. We analyze each of these categories of ethical issues and provide policy approaches for addressing them.     

Clinical manifestations and stages of Rett syndrome

The presentation and clinical diagnosis of Rett syndrome at various ages and stages are reviewed. In addition to the classical form, variability in phenotype between different atypical Rett forms is given. Obligatory, supportive, and differential diagnostic criteria are summarized. Long-term follow-up findings in ageing Rett women are addressed.     

Additional study of the Youth-Depression Adjective Check List

Replicated and extended aspects of determinations of reliability and validity for the State version of the Youth-Depression Adjective Check List. Students from Grades 9 through 12 (64 girls and 41 boys) completed the State version and the Adolescent Activities Checklist on each of 12 consecutive days and completed the Trait version, the Reynolds Adolescent Depression Scale, the Multiple Affect Adjective Check List--Revised Grade 6, and the Adolescent Activities Checklist at the beginning and the end of the study. Good reliability and validity of the State version were confirmed and extended, and preliminary information on characteristics of the Trait version of the Youth-Depression Adjective Check List also was presented. The State version seems suitable for use in research with adolescents and preadolescents. More study of the Trait version is recommended.     

Color discrimination under chronic hypoxic conditions (simulated climb "Everest-Comex 97")

Hypoxia is known to alter visual functions. In the present study, the effects of chronic hypobaric hypoxia upon visual color discrimination were studied in 8 subjects participating in a simulated climb from sea level (PO2 = 210 hPa) to 8,848 m (PO2 = 70 hPa) over a 31-day period of confinement in a decompression chamber ('Everst-Comex 97'). During these investigations, the subjects were required to discriminate between colors of different hue in the red, blue, and green ranges. Alterations in color discrimination increased slightly but significantly as altitude increased. Impairments occurred mainly in the red and blue ranges. In addition, our results further indicate that color discrimination would be affected only when a minimum threshold of difference between color stimuli is not present. Methodological and physiological implications are discussed.     

Effects of differences in timbre on sequential grouping

Differences in the timbre of sounds in a sequence can affect their perceptual organization. Using a performance measure, Hartmann and Johnson (1991) concluded that streaming could be predicted primarily by the extent to which sounds were passed by different peripheral channels. However, results from a rating task by Dannenbring and Bregman (1976) suggested that sounds in the same spectral region (passed by the same peripheral channels) can be allocated to different streams. In Experiment 1, it was found, using an interleaved melody task, that target sounds could be selected from distractors in the same spectral region more easily when they differed in timbre. This finding might result from primitive stream segregation or schema-driven selection, but not from peripheral channeling. In Experiment 2, a rhythm discrimination task was used, requiring the sounds to be integrated for good performance. Differences in timbre impaired performance, indicating the occurrence of primitive stream segregation.     

Assessment of weight and eating concerns in Norwegian adolescents

The aim of the present study was to test the properties of an instrument that assesses concerns about weight and eating without reference to dieting behavior. A short instrument, the Weight and Eating Concerns Inventory (WECI) was examined in a sample of 569 boys and 548 girls aged 11 to 15 years. Confirmatory factor analyses with LISREL showed a better fit with a version of the instrument that did not include a reference to dieting behavior, compared to a version that included such a reference. This was true for both boys and girls, irrespective of their age group. However, the results indicated that both versions should be used with caution for young boys. The internal consistency of the WECI (that is, the version without reference to dieting) was satisfactory, ranging from 0.78 to 0.86 for girls and from 0.68 to 0.73 for boys. The WECI correlated quite substantially with negative self-evaluations and depression for boys and girls in all the age groups assessed, suggesting that high scores on the WECI may indicate a problem that goes beyond worries or concerns, and should be taken seriously. In general, girls reported more of these concerns than boys, and the correlation between the WECI and dieting was stronger among girls compared to boys.     

Psychosocial Treatment Strategies in the MTA Study: Rationale, Methods, and Critical Issues in Design and Implementation

The Collaborative Multimodal Treatment Study of Children with Attention Deficit Hyperactivity Disorder (ADHD), the MTA, is the first multisite, cooperative agreement treatment study of children, and the largest psychiatric/psychological treatment trial ever conducted by the National Institute of Mental Health. It examines the effectiveness of Medication vs. Psychosocial treatment vs. their combination for treatment of ADHD and compares these experimental arms to each other and to routine community care. In a parallel group design, 579 (male and female) ADHD children, aged 7–9 years, 11 months, were randomly assigned to one of the four experimental arms, and then received 14 months of prescribed treatment (or community care) with periodic reassessments. After delineating the theoretical and empirical rationales for Psychosocial treatment of ADHD, we describe the MTA's Psychosocial Treatment strategy applied to all children in two of the four experimental arms (Psychosocial treatment alone; Combined treatment). Psychosocial treatment consisted of three major components: a Parent Training component, a two-part School Intervention component, and a child treatment component anchored in an intensive Summer Treatment Program. Components were selected based on evidence of treatment efficacy and because they address comprehensive symptom targets, settings, comorbidities, and functional domains. We delineate key conceptual and logistical issues faced by clinical researchers in design and implementation of Psychosocial research with examples of how these issues were addressed in the MTA study.Deceased     

Parenting and Family Stress Treatment Outcomes in Attention Deficit Hyperactivity Disorder (ADHD): An Empirical Analysis in the MTA Study

Parenting and family stress treatment outcomes in the MTA study were examined. Male and female (579), 7–9-year-old children with combined type Attention Deficit Hyperactivity Disorder (ADHD), were recruited at six sites around the United States and Canada, and randomly assigned to one of four groups: intensive, multi-faceted behavior therapy program alone (Beh); carefully titrated and monitored medication management strategy alone (MedMgt); a well-integrated combination of the two (Comb); or a community comparison group (CC). Treatment occurred over 14 months, and assessments were taken at baseline, 3, 9, and 14 months. Parenting behavior and family stress were assessed using parent-report and child-report inventories. Results showed that Beh alone, MedMgt alone, and Comb produced significantly greater decreases in a parent-rated measure of negative parenting, Negative/Ineffective Discipline, than did standard community treatment. The three MTA treatments did not differ significantly from each other on this domain. No differences were noted among the four groups on positive parenting or on family stress variables. Results are discussed in terms of the theoretical and empirically documented importance of negative parenting in the symptoms, comorbidities and long-term outcomes of ADHD.     

The development of children's knowledge of attention and resource allocation in single and dual tasks

Developmental changes in kindergarten, 1st-, and 4th-grade children's knowledge about the variables that affect attention sharing and resource allocation were examined. Findings from the 2 experiments showed that kindergartners understood that person and strategy variables affect performance in attention-sharing tasks. However, knowledge of how task variables affect performance was not evident to them and was inconsistent for 1st and 4th graders. Children's knowledge about resource allocation revealed a different pattern and varied according to the dissimilarity of task demands in the attention-sharing task. In Experiment 1, in which the dual attention tasks were similar (i.e., visual detection), kindergarten and 1st-grade children did not differentiate performance in single and dual tasks. Fourth graders demonstrated knowledge that performance on a single task would be better than performance on the dual tasks for only 2 of the variables examined. In Experiment 2, in which the dual attention tasks were dissimilar (i.e., visual and auditory detection), kindergarten and 1st-grade children demonstrated knowledge that performance in the single task would be better than in the dual tasks for 1 of the task variables examined. However, 4th-grade children consistently gave higher ratings for performance on the single than on the dual attention tasks for all variables examined. These findings (a) underscore that children's meta-attention is not unitary and (b) demonstrate that children's knowledge about variables affecting attention sharing and resource allocation have different developmental pathways. Results show that knowledge about attention sharing and about the factors that influence the control of attention develops slowly and undergoes reorganization in middle childhood.