RNA interference: a new mechanism by which FMRP acts in the normal brain? What can Drosophila teach us?

Fragile X syndrome is the most common heritable form of mental retardation caused by loss-of-function mutations in the FMR1 gene. The FMR1 gene encodes an RNA-binding protein that associates with translating ribosomes and acts as a negative translational regulator. Recent work in Drosophila melanogaster has shown that the fly homolog of FMR1 (dFMR1) plays an important role in regulating neuronal morphology, which may underlie the observed deficits in behaviors of dFMR1 mutant flies. Biochemical analysis has revealed that dFMR1 forms a complex that includes ribosomal proteins and, surprisingly, Argonaute2 (AGO2), an essential component of the RNA-induced silencing complex (RISC) that mediates RNA interference (RNAi) in Drosophila. dFMR1 also associates with Dicer, another essential processing enzyme of the RNAi pathway. Moreover, both a micro-RNA (miRNA) and short interfering RNAs (siRNAs) can coimmunoprecipitate with dFMR1. Together these findings suggest that dFMR1 functions in an RNAi-related apparatus to regulate the expression of its target genes at the level of translation. These findings raise the possibility that Fragile X syndrome may be the result of a protein synthesis abnormality caused by a defect in an RNAi-related apparatus. Because the core mechanisms of complex behaviors such as learning and memory and circadian rhythms appear to be conserved, studies of Fragile X syndrome using Drosophila as a model provide an economy-of-scale for identifying biological processes that likely underlie the abnormal morphology of dendritic spines and behavioral disturbances observed in Fragile X patients.     

Understanding pretrial publicity: predecisional distortion of evidence by mock jurors

Prejudicial pretrial publicity (PTP) constitutes a serious source of juror bias. The current study examined differences in predecisional distortion for mock jurors exposed to negative PTP (N-PTP) versus nonexposed control participants. According to work by K. A. Carlson and J. E. Russo (2001), predecisional distortion occurs when jurors bias new evidence in favor of their current leading party (prosecution or defense) rather than evaluating this information for its actual probative properties. Jury-eligible university students (N=116) acted as jurors in a mock trial. Elevated rates of guilty verdicts were observed in the N-PTP condition. Predecisional distortion scores were significantly higher in the N-PTP condition and reflected a proprosecution bias. The effect of prejudicial PTP on verdict outcomes was mediated by predecisional distortion in the evaluation of testimony. Results are discussed in relation to motivated decision making and confirmation biases.     

Comorbidity in compulsive hoarding: a case report

A 56-year-old male presented with compulsive hoarding along with attention-deficit/hyperactivity disorder and schizotypal personality disorder. Hoarding has been described as difficult to treat both pharmacologically and behaviorally, and this patient's comorbid conditions also contributed to his overall impairment. The patient's treatment regimen of fluvoxamine, amphetamine salts, and risperidone, along with behavioral therapy, has helped with hoarding behaviors, motivation, procrastination, and increased socialization. Hoarding may be a unique subtype of obsessive-compulsive disorder with poorer prognosis and distinct neuroanatomic dysfunction. Augmentation with stimulants may provide benefits in aspects of hoarding such as procrastination, especially in patients with comorbid attention-deficit hyperactivity disorder.     

Government initiatives in autism clinical trials

Randomized clinical trials remain the most valid method of testing the efficacy and safety of treatments. While efforts to elucidate the genetic and neurodevelopmental bases of autism are underway, clinicians and families are in need of scientifically valid information on how to best treat patients with autism. The effectiveness of many interventions currently used in communities has not been adequately tested. Given the high public health relevance of autism treatment research and the low interest of the pharmaceutical industry in autism, the role of the National Institutes of Health in supporting this research is paramount. Among recently launched initiatives in autism clinical trials, there are the Research Units on Pediatric Psychopharmacology Autism Network and the network of centers for Studies to Advance Autism Research and Treatment. These and other government activities in the area of autism clinical trials are here briefly reviewed.     

Impact of recent findings on study design of future autism clinical trials

There are specific challenges to studying the design of pharmacologic trials in child/adolescent and adult autism, such as subject stratification and parallel versus crossover designs. This article describes how optimal study design is influenced by subject selection and outcome measures chosen. Lessons learned in study design from the Research Units on Pediatric Psychopharmacology Autism Network trial with risperidone, Seaver Center trials with fluoxetine and valproate, Dartmouth trials with amantadine, and National Institutes of Health secretin trials are highlighted. The Internet System for Assessing Autistic Children system for managing multicenter clinical trials in autism and statistical issues in autism research are also described.     

A longitudinal study of gender-related cognition and behaviour

Gender schema theory proposes that children's acquisition of gender labels and gender stereotypes informs gender-congruent behaviour. Most previous studies have been cross-sectional and do not address the temporal relationship between knowledge and behaviour. We report the results of a longitudinal study of gender knowledge and sex-typed behaviour across three domains in children tested at 24 and 36 months (N = 56). Although both knowledge and sex-typed behaviour increased significantly between 2 and 3 years, there was no systematic pattern of cross-lagged correlations between the two, although some concurrent relationships were present at 24 months. Future longitudinal work might profitably focus on younger children using reliable preverbal measures of gender knowledge and employing a shorter lag between measurement times.     

Informed consent and the use of placebo in poland: Ethical and legal aspects

The concept of informed consent was one of the most fruitful ideas that deeply changed the relationships between physicians and their patients from paternalism to respect for the personal autonomy of subjects needing professional medical care. The great progress in medicine, also involving the pharmaceutical industry, has created an increasing need to perform different clinical and experimental trials. The evolution of clinical research in the last decades has influenced strongly the design of these studies. One of the most important changes in this field has been the use of placebo groups in double-blind controlled studies. The controversies have involved not only the use of placebo when standard or proven treatment was available, but also some specific problems concerning the procedure of obtaining informed consent in such trials. This paper briefly presents the evolution of informed consent in Poland as well as different ethical and legal problems concerning informed consent and the use of placebo controls in clinical trials. An earlier version of this paper was presented at an international conference, “Placebo: Its Action and Place in Health Research Today,” held in Warsaw, Poland on 12–13 April, 2003.