Unintended changes in cognition, mood, and behavior arising from cell-based interventions for neurological conditions: ethical challenges.

The prospect of using cell-based interventions (CBIs) to treat neurological conditions raises several important ethical and policy questions. In this target article, we focus on issues related to the unique constellation of traits that characterize CBIs targeted at the central nervous system. In particular, there is at least a theoretical prospect that these cells will alter the recipients' cognition, mood, and behavior-brain functions that are central to our concept of the self. The potential for such changes, although perhaps remote, is cause for concern and careful ethical analysis. Both to enable better informed consent in the future and as an end in itself, we argue that early human trials of CBIs for neurological conditions must monitor subjects for changes in cognition, mood, and behavior; further, we recommend concrete steps for that monitoring. Such steps will help better characterize the potential risks and benefits of CBIs as they are tested and potentially used for treatment.

Cell-based interventions for neurologic conditions: ethical challenges for early human trials.

BACKGROUND: Attempts to translate basic stem cell research into treatments for neurologic diseases and injury are well under way. With a clinical trial for one such treatment approved and in progress in the United States, and additional proposals under review, we must begin to address the ethical issues raised by such early forays into human clinical trials for cell-based interventions for neurologic conditions. METHODS: An interdisciplinary working group composed of experts in neuroscience, cell biology, bioethics, law, and transplantation, along with leading disease researchers, was convened twice over 2 years to identify and deliberate on the scientific and ethical issues raised by the transition from preclinical to clinical research of cell-based interventions for neurologic conditions. RESULTS: While the relevant ethical issues are in many respects standard challenges of human subjects research, they are heightened in complexity by the novelty of the science, the focus on the CNS, and the political climate in which the science is proceeding. CONCLUSIONS: Distinctive challenges confronting US scientists, administrators, institutional review boards, stem cell research oversight committees, and others who will need to make decisions about work involving stem cells and their derivatives and evaluate the ethics of early human trials include evaluating the risks, safety, and benefits of these trials, determining and evaluating cell line provenance, and determining inclusion criteria, informed consent, and the ethics of conducting early human trials in the public spotlight. Further study and deliberation by stakeholders is required to move toward professional and institutional policies and practices governing this research.

Religious and philosophical exemptions from vaccination requirements and lessons learned from conscientious objectors from conscription.

All jurisdictions in the US require proof of vaccination for school entrance. Most states permit non-medical exemptions. Public health officials must balance the rights of individuals to choose whether or not to vaccinate their children with the individual and societal risks associated with choosing not to vaccinate (i.e., claiming an exemption). To assist the public health community in optimally reaching this balance, this analysis examines the constitutional basis of non-medical exemptions and examines policies governing conscientious objection to conscription as a possible model. The jurisprudence that the US Supreme Court has developed in cases in which religious beliefs conflict with public or state interests suggests that mandatory immunization against dangerous diseases does not violate the First Amendment right to free exercise of religion. Accordingly, states do not have a constitutional obligation to enact religious exemptions. Applying the model of conscientious objectors to conscription suggests that if states choose to offer nonmedical exemptions, they may be able to optimally balance individual freedoms with public good by considering the sincerity of beliefs and requiring parents considering exemptions to attend individual educational counseling.

Problem behavior: the double symptom of adolescence.

In this article we address several issues regarding problem or antisocial behavior in adolescents. First, we discuss conceptualizations of adolescent problem behavior to answer the question 'What do we think we know so far?" Then, we briefly characterize current interventions designed to reduce these behaviors, and their relative success in doing so. Next, we examine earlier attempts to prevent and ameliorate problem behavior (including juvenile delinquency), situating them in the historical context of America from the turn of the century to World War II. Here, we attempt to answer the questions "How did we get to where we are?" and "How can we learn from the past?" Following this, we try to answer the question "Where do we go from here?" and articulate some research and policy implications relevant to developmental psychopathology that arise from these considerations. We argue that problem behavior is viewed most productively in its double aspect, which John Hughlings Jackson called a "double symptom," with the positive aspect of the symptom reflecting adolescents' attempts to satisfy their developmental needs.

Risk-taking patterns of female adolescents: what they do and why.

A total of 58 college-age adolescent females were asked to provide information about their risk-taking behaviors. Participants completed a risk-taking questionnaire and were asked to keep a diary of their risk-taking behaviors for 1 week. Participants were also asked to provide reasons for engaging in each behavior they listed. Results indicated that participants engaged in a variety of risky behaviors ranging from traditional adolescent risk-taking behaviors, e.g. drinking and sex, to other behaviors not typically included in studies of risk-taking, e.g. interpersonal and financial risky behaviors. An analysis of the justifications given for engaging in the various behaviors were largely goal-oriented (e.g. engaging in a behavior as a means to an end) or reflected a preoccupation with personal needs (e.g. engaging in a behavior to relieve loneliness or stress). These results are contrary to the widely held belief that adolescents' risk-taking is "mindless," "aimless," or mere "sensation seeking."

Late adolescent risk-taking: effects of perceived benefits and perceived risks on behavioral intentions and behavioral change.

To assess the predictive utility of perceived benefits and risks of risk-taking behaviors (RTBs) on behavioral intentions and behavioral change, data were collected from 187 male and female late adolescent college students (ages 17-20). Perceived benefits, perceived risks, behavioral intentions, and involvement for 18 RTBs were assessed at T1 and T2 (3 months later). Factor analyses were performed on T1 involvement data, and six RTB factors emerged: Alcohol RTBs, Illegal Drug RTBs, Stereotypic Male RTBs, Social RTBs, Sex RTBs, and Imprudent RTBs. Regression analyses indicated that perceived benefits accounted for significant variance in behavioral intentions for each of the six factors and Overall RTB; perceived risks accounted for significant variance in behavioral intentions for five of the factors. Similar regression analyses indicated that perceived benefits accounted for significant variance in behavior change (over a 3 month period) for each of the six factors and the Overall RTB score, whereas perceived risks accounted for significant variance for only one factor (Illegal Drug RTBs). The result suggest that, among late adolescents, perceived benefits are better determinants of behavior change for RTBs than are perceived risks. Both perceived benefits and perceived risks, however, are important determinants of behavioral intentions. These findings support previous work identifying adolescents as "sensation seekers". Interventions should address perceived benefits of RTB, rather than relying solely on promoting knowledge of the risks. Assessment of adolescent RTB should continue to use multi-item measures to obtain a broad picture of the variety of behaviors commonly endorsed by adolescents.

Developing conceptions of chronic disease: a comparison of disease experience.

We predicted that children's conceptions of various self-care behaviors and social relations would be related to their degree of experience with insulin-dependent diabetes mellitus (IDDM). A total of 55 children were recruited for this study in three experience groups: children with IDDM (high experience), children having a sibling with IDDM (low experience), and normal healthy children (no experience). In line with our model, children with IDDM had a more developed and sophisticated understanding of concepts associated with disease management than did either siblings of children with diabetes or the comparison group; surprisingly, experience with the disease (children with IDDM) was associated with more complex conceptions of social relations as well.

Adolescent risk-taking: an analysis of problem behaviors in problem children.

In this study adolescent risk-taking is explored from several theoretical positions: Jessor's problem-behavior perspective, risk-taking as normal and adaptive, adolescent egocentrism, and a decision-making perspective. Adolescents (ages 11-17) referred to mental health clinics (N = 80) completed a risk involvement and perception questionnaire, the Jesness Personality Inventory, and a measure of adolescent egocentrism. For purposes of concurrent validity, a diagnosis was completed by the subject's clinic therapist. As predicted, both Benefit and Risk Perception were significantly correlated with Involvement (in opposite directions), supportive of a decision-making perspective. A configuration of social maladjustment personality correlates in conjunction with a diagnosis of Conduct Disorder showed a strong, positive correlation with Involvement, supporting a problem-behavior perspective. Egocentrism measures were not significantly related to Risk Involvement or Risk and Benefit Perceptions. Adolescent risk-taking is argued to be a multidimensional phenomenon involving personality correlates and cognitive aspects of decision-making.

Attributional style and self-control behavior in depressed and nondepressed children and their parents.

Do the reformulated model of learned helplessness and the self-control model apply to clinically depressed children? Are the related cognitive patterns specific to depression? Are the cognitive deficits associated with depression learned from one's parents? To address these questions this investigation examined three groups of children (ages 8-12) and their parents: nonclinic (n = 25), nondepressed clinic (n = 22), and depressed clinic (n = 15). Children were diagnosed depressed on the basis of Kiddie-SADS interview data. Depressed clinic children self-reported more depression, had a more depressive attributional style, and had more self-control problems. There were more depressed mothers in the clinic than in the nonclinic sample. Depressed clinic children had more depressed mothers than did nondepressed clinic children. There were no differences among the three groups of parents in their cognitive patterns. No relationship was found between the attributional style and self-control behavior of children and their parents.

Social-cognitive and cognitive correlates of depression in children.

The present investigation examined depression and its social-cognitive and cognitive correlates in a sample of 108 elementary school children: 36 children in each of grades 1, 4, and 8. Children were classified as depressed and nondepressed according to their scores on the Children's Depression Inventory (CDI). Depression appeared stable over a 3-week time interval. Depressed children reported a higher number of "masking" symptoms, were rated as more depressed by their teachers, and perceived their family environment to be more distressed. As posited, when compared to nondepressed children, depressed children have lower self-esteem, a more depressive attributional style, and more self-control deficits. Further, they have impaired performance on some cognitive tasks (block design, coding digit span) but not all (vocabulary). The prediction that depression would be manifested differently in first-, fourth-, and eighth-graders was not supported.

Way finding and cognitive mapping in large-scale environments: a test of a developmental model.

First, fourth, and seventh graders (7, 10, and 13 years of age, respectively) were given a series of tasks to assess their spatial competency in and their cognitive mapping of their school campus. Measures of way-finding, landmark, route, and configurational knowledge were obtained and analyzed to (1) assess way-finding skills in the same environment as that in which their cognitive representations were inferred and assessed; (2) determine the validity of the hierarchical model of cognitive mapping development proposed by Siegel and White by examining individual children's performance patterns as well as between-group performance; and (3) investigate the relationship between grade level and familiarity within an environment where familiarity within subsets of the environment varied by grade. Subjects were asked to create and walk three novel and efficient routes, to select photographs of scenes belonging to the three routes, to correctly order and metrically relate those scenes, and to make bearing and distance estimates from four sighting locations to six targets within the environment. Results indicated that all children were extremely competent way finders. Guttman scale analysis revealed that 93% of all children exhibited performance patterns predicted by the proposed model. Further support of the model was found in grade level differences on cognitive mapping measures. Reversals in the developmental trend were found, however, on some portions of the route and configuration measures, and were significantly related to degree of familiarity within the environment.

Developmental issues in cognitive mapping: the selection and utilization of environmental landmarks.

2 studies were conducted to investigate developmental differences in the ability to select and use environmental landmarks for cognitively organizing distance information from a walk. In experiment 1, second-grade, fifth-grade, and college subjects viewed a simulated walk and selected scenes that were high in potential landmark value. In experiment 2, children from the same grade levels first viewed the walk and then ranked distances among either the test scenes most frequently selected by their peers or those selected most frequently by adults. Results indicated that (a) adults and children may not spontaneously select the same features as real-world landmarks; (b) children are less capable than adults in judging the value of potential landmarks as distance cues; and (c) the ability to use environmental landmarks as cues for distance information developmentally precedes the ability to assess this potential information value.

The development of cognitive maps of large- and small-scale spaces.

Kindergartners, second, and fifth graders made repeated trips through a large- or small-scale model town, and then constructed from memory the layout of buildings in either a large- or small-scale space. Accuracy of construction increased as a function of developmental level and repeated trips through the town. Children's constructions were most accurate when they were tested in the same-scale environment as that in which they developed their spatial knowledge; accuracy was impaired significantly only when children were exposed to a small space and then reconstructed in a large space. Results were interpreted in terms of a "competence-load trade-off."

Sex and hemispheric differences in the recall of verbal and spatial information.

Arrays of four digits were presented in a 3 X 3 matrix for 80 msec to either the left or right visual field. Women recalled digits presented to the left and right visual fields equally well, while men recalled digits more accurately after presentation to the right visual field. Both men and women recalled the positions of the digits presented to the left and right visual fields equally well. Overall, men's recall of positions was superior to that of women. Handedness correlated only with recall of positions presented to the right visual field, positively for women and negatively for men.