Employees' perspectives on ethically important aspects of genetic research participation: a pilot study

PURPOSE: Insights from genetic research may greatly improve our understanding of physical and mental illnesses and assist in the prevention of disease. Early experience with genetic information suggests that it may lead to stigma, discrimination, and other psychosocial harms, however, and this may be particularly salient in some settings, such as the workplace. Despite the importance of these issues, little is known about how healthy adults, including workers, perceive and understand ethically important issues in genetic research pertaining to physical and mental illness. METHOD: We developed, pilot tested, and administered a written survey and structured interview to 63 healthy working adults in 2 settings. For this paper, we analyzed a subset of items that assessed attitudes toward ethically relevant issues related to participation in genetic research on physical and mental illness, such as its perceived importance, its acceptability for various populations, and appropriate motivations for participation. RESULTS: Our respondents strongly endorsed the importance of physical and mental illness genetic research. They viewed participation as somewhat to very acceptable for all 12 special population groups we asked about, including persons with mental illness. They perceived more positives than negatives in genetic research participation, giving neutral responses regarding potential risks. They affirmed many motivations for participation to varying degrees. Men tended to affirm genetic research participation importance, acceptability, and motivations more strongly than women. CONCLUSION: Healthy working persons may be willing partners in genetic research related to physical and mental illnesses in coming years. This project suggests the feasibility and value of evidence-based ethics inquiry, although further study is necessary. Evidence regarding stakeholders' perspectives on ethically important issues in science may help in the development of research practices and policy.     

Neurodevelopmental implications of ocular motor apraxia

Ocular motor apraxia (OMA), a disorder of saccadic initiation, may be congenital or acquired. While the acquired form is frequently associated with significant neuropathology, the congenital form is often regarded as relatively benign. Many children with congenital OMA who were observed clinically have shown neurodevelopmental disturbance over time. A retrospective review was taken of 34 consecutive patients (22 males and 12 females), seen over a 20-year period, to evaluate the frequency and type of associated neurodevelopmental problems. Age at presentation ranged from 8 weeks to 14 years, with a mean age of 10 years. Of 29 children with congenital OMA, 15 had imaging evidence of structural central nervous system abnormalities (with cerebellar hypoplasia the most frequent abnormality detected). Eleven of the 14 patients with no structural abnormality showed abnormal neurodevelopment. This study suggests that congenital OMA is not a benign diagnosis, even in the absence of overt neurological disturbance at the time of presentation.     

Sensorimotor gating, orienting and social perception in schizophrenia

Basic neurocognition and social cognition appear to influence the social impairments of persons with schizophrenia. This study examined relationships between two very basic automatic processes (i.e., sensorimotor gating and orienting) and social perception in schizophrenic patients. Thirty outpatients with schizophrenia completed psychophysiological measures of sensorimotor gating (prepulse inhibition, PPI), orienting (prepulse facilitation, PPF), and social perception (the Half Profile of Nonverbal Sensitivity, Half PONS). A median split was used to divide patients into poor and good gaters and poor and good orienters. Analyses revealed that patients with good PPI scored significantly higher on the Half PONS than patients with poor PPI. PPI showed a significant correlation (r=-0.54) with Half PONS performance, indicating that schizophrenia patients who were better able to gate out competing stimuli (i.e., less startle) were also better at detecting relevant social cues. Orienting (PPF) and social perception were not related. This study is the first to our knowledge to demonstrate an association between sensorimotor gating and social perception. The findings are consistent with other studies that have demonstrated relationships between basic neurocognition and social cognition. By showing a link between sensorimotor gating and social perception, this study supports social cognition's potential role as a mediator of the relationship between neurocognition and social functioning in schizophrenia.     

Independent effects of tobacco abstinence and bupropion on cognitive function in schizophrenia

OBJECTIVE: The objective of this study was to examine the effects of tobacco abstinence and bupropion treatment on cognitive functioning in adult smokers with schizophrenia in the setting of a randomized, double-blind, placebo-controlled clinical trial of bupropion for smoking cessation. METHOD: Fifty-three adults with schizophrenia (DSM-IV) took part in a trial of bupropion for smoking cessation. Subjects were enrolled in the study from August 1999 to March 2003. Forty-five subjects remained in the trial at week 4; 41 subjects, 19 taking bupropion and 22 taking placebo, completed the baseline and week 4 cognitive assessments and were included in the analysis of adjusted effects of abstinence and bupropion treatment on cognitive function. RESULTS: Controlling for bupropion treatment and baseline performance, 7 days of tobacco abstinence was associated with slowed motor speed (finger tapping) but was not associated with worsening of performance on tests of attention (AX Continuous Performance Test [AX-CPT]), verbal learning and memory (California Verbal Learning Test [CVLT]), working memory (digit span), or executive function/inhibition (Stroop) and was not associated with worsening of any clinical measures. Controlling for abstinence status, bupropion was associated with reduction (improvement) in reaction time variability on the AX-CPT and with reduction in perseverative errors on the CVLT. CONCLUSION: We conclude that 1 week of tobacco abstinence is associated with slowed motor speed but is not associated with detectable worsening in performance on a range of neuropsychological tests or clinical symptoms in the subset of patients who were able to quit smoking. We also conclude that bupropion treatment may be associated with improvement in variability of attention.     

Monocyte derived dendritic cell responses in common variable immunodeficiency

The phenotype and function of monocyte derived dendritic cells (MdDC) were investigated in 25 patients with common variable immunodeficiency (CVID) to test for abnormalities that might help explain the failure of antibody production. Using MHC class II DR and CD86 as markers of maturation, DCs from the majority of CVID patients were normal. However 5 patients, the majority of whom had affected family members who had previously been shown to have a susceptibility genetic locus in the MHC region, expressed abnormally low levels of DR on repeated testing, in some cases associated with a reduced capacity to support antigen stimulated T cell proliferation; nevertheless costimulatory molecules for production of IL-13, IL-10 and IFN-gamma from T cells were intact. In contrast to DCs from healthy donors, DCs from many CVID patients had high spontaneous production of IL-8 and lipopolysaccharide stimulation often caused a reduction in DR expression. Expression of other cytokines (IL-1a, IL-6 and IL-12), either before or after LPS stimulation, was normal. The data suggests there is a fundamental defect in the maturation of MdDCs in a subset of CVID patients that may compromise antigen presentation and subsequent antibody production.     

A new social communication intervention for children with autism: pilot randomised controlled treatment study suggesting effectiveness

BACKGROUND: Psychosocial treatments are the mainstay of management of autism in the UK but there is a notable lack of a systematic evidence base for their effectiveness. Randomised controlled trial (RCT) studies in this area have been rare but are essential because of the developmental heterogeneity of the disorder. We aimed to test a new theoretically based social communication intervention targeting parental communication in a randomised design against routine care alone. METHODS: The intervention was given in addition to existing care and involved regular monthly therapist contact for 6 months with a further 6 months of 2-monthly consolidation sessions. It aimed to educate parents and train them in adapted communication tailored to their child's individual competencies. Twenty-eight children with autism were randomised between this treatment and routine care alone, stratified for age and baseline severity. Outcome was measured at 12 months from commencement of intervention, using standardised instruments. RESULTS: All cases studied met full Autism Diagnostic Interview (ADI) criteria for classical autism. Treatment and controls had similar routine care during the study period and there were no study dropouts after treatment had started. The active treatment group showed significant improvement compared with controls on the primary outcome measure--Autism Diagnostic Observation Schedule (ADOS) total score, particularly in reciprocal social interaction--and on secondary measures of expressive language, communicative initiation and parent-child interaction. Suggestive but non-significant results were found in Vineland Adaptive Behaviour Scales (Communication Sub-domain) and ADOS stereotyped and restricted behaviour domain. CONCLUSIONS: A Randomised Treatment Trial design of this kind in classical autism is feasible and acceptable to patients. This pilot study suggests significant additional treatment benefits following a targeted (but relatively non-intensive) dyadic social communication treatment, when compared with routine care. The study needs replication on larger and independent samples. It should encourage further RCT designs in this area.