From complexity to category: Responding to diagnostic uncertainties of autistic spectrum disorders

Objective: Recent data from Education Queensland has identified rising numbers of children receiving diagnoses of autistic spectrum disorder (ASD). Faced with funding diagnostic pressures, in clinical situations that are complex and inherently uncertain, it is possible that specialists err on the side of a positive diagnosis. This study examines the extent to which possible overinclusion of ASD diagnosis may exist in the presence of uncertainty and factors potentially related to this practice in Queensland. Methods: Using anonymous self-report, all Queensland child psychiatrists and paediatricians who see paediatric patients with development/behavioural problems were surveyed and asked whether they had ever specified an ASD diagnosis in the presence of diagnostic uncertainty. Using logistic regression, elicited responses to the diagnostic uncertainty questions were related to other clinical- and practice-related characteristics. Results: Overall, 58% of surveyed psychiatrists and paediatricians indicated that, in the face of diagnostic uncertainty, they had erred on the side of providing an ASD diagnosis for educational ascertainment and 36% of clinicians had provided an autism diagnosis for Carer's Allowance when Centrelink diagnostic specifications had not been met. Conclusion: In the absence of definitive biological markers, ASD remains a behavioural diagnosis that is often complex and uncertain. In response to systems that demand a categorical diagnostic response, specialists are providing ASD diagnoses, even when uncertain. The motivation for this practice appears to be a clinical risk/benefit analysis of what will achieve the best outcomes for children. It is likely that these practices will continue unless systems change eligibility to funding based on functional impairment rather than medical diagnostic categories.

The ins and outs of transcriptional control: nucleocytoplasmic shuttling in development and disease

Recent findings relating to SOX transcription factors indicate that defects in organogenesis can be caused not only by impairment of the biochemical properties of transcription factors but also, in some cases, by deficient nuclear import. In addition, experimentally interfering with the nuclear export signals of some SOX factors has now been found to cause developmental defects. Controlling the balance of nuclear import and export might be a common means by which transcription factor activity can be regulated during development, and defects in these processes might underlie a broader spectrum of inherited developmental disorders.

Mind and body: Concepts of human cognition, physiology and false belief in children with autism or typical development

This study examined theory of mind (ToM) and concepts of human biology (eyes, heart, brain, lungs and mind) in a sample of 67 children, including 25 high functioning children with autism (age 6-13), plus age-matched and preschool comparison groups. Contrary to Baron-Cohen [1989, Journal of Autism and Developmental Disorders, 19(4), 579-600], most children with autism correctly understood the functions of the brain (84%) and the mind (64%). Their explanations were predominantly mentalistic. They outperformed typically developing preschoolers in understanding inner physiological (heart, lungs) and cognitive (brain, mind) systems, and scored as high as age-matched typical children. Yet, in line with much previous ToM research, most children with autism (60%) failed false belief, and their ToM performance was unrelated to their understanding of. human biology. Results were discussed in relation to neurobiological and social-experiential accounts of the ToM deficit in autism.

Anxiety and social worries in children with Asperger syndrome

Objective: The current study examined anxiety and social worries in a group of children with Asperger syndrome (AS). Method: Sixty-five children with AS were compared with a clinically anxious sample and a normative sample using parent and child reports. Results: Comparisons between clinically anxious children and children with AS showed similar scores on overall anxiety and on six anxiety subscales using child reports. Parent reports revealed higher ratings of overall anxiety and described children with AS experiencing more obsessive-compulsive symptoms and physical injury fears than clinically anxious children. Conclusions: Children with AS without a diagnosis of anxiety, present with more anxiety symptoms than a normal population and with a different profile than a clinically anxious population. Study limitations are identified and considerations for future research presented.

Training school personnel to implement a universal school-based prevention of depression program under real-world conditions

The present study evaluated the impact of a universal prevention of depression program [the Resourceful Adolescent Program (RAP)] when implemented under real-world conditions in a school setting. Prior research has found the RAP program to be beneficial for high-school students when the program was implemented by university staff selected, trained, and supervised by a research team. The present study evaluated the RAP program when implemented by existing school personnel. Separately, we measured the impact of a training program for facilitators, the quality of subsequent program implementation, and the student's response to the RAP Program. Results showed that, in response to the training program, facilitators believed they had acquired the knowledge and confidence to implement the program and that the quality of program implementation was acceptable. The study did not demonstrate a beneficial impact of the RAP program for the students. The results raise important questions regarding the extent of training and ongoing supervision facilitators require if the beneficial outcomes for students are to be maintained when interventions are implemented under real-world conditions in school settings. (C) 2004 Society for the Study of School Psychology. Published by Elsevier Ltd. All rights reserved.

Identifying and predicting adolescent smokers' developmental trajectories

Very few studies have defined trajectories of smoking. In the present study, we modeled growth in adolescent smoking and empirically identified prototypical trajectories. We conceptualized escalation of smoking as a growth process and modeled rates of change and heterogeneity of these patterns using latent growth mixture modeling. The analysis identified six trajectories with low ambiguity about group membership (early rapid escalators, late rapid escalators, late moderate escalators, late slow escalators-smokers, stable puffers, and late slow escalators-puffers). A trajectory of quitters was not identified. We also examined predictors of the smoking trajectories. The predictors were assessed across the adolescent years and included variables related to smoking and other substance use, as well as a range of variables related to sociodemographic factors and mental health. Observed change in the pattern of predictors across age has implications for the mechanism of effect of these variables in relation to smoking trajectories, including predictors that differentiated among daily smokers, variables that may determine the trajectory (e.g., friends smoking), and variables that may result from the trajectory (e.g., marijuana use, less attachment to friends).

Prevention of Cervical Cancer Through Papillomavirus Vaccination

A subset of human papillomaviruses (HPVs) promote anogenital malignancy, including cervical cancer, and prevention and treatment strategies that reflect the causal role of HPV are being developed. Vaccines based on HPV virus-like particles induce genotype-specific virus-neutralizing antibody and prevent infection with HPV1. Persistent papillomavirus infection is required for the development of papillomavirus-associated cancer and, therefore, therapeutic vaccines are being developed to eliminate established papillomavirus infection. Such vaccines test principles for the growing field of tumour-antigen-specific immunotherapy. This article reviews progress in the field and draws conclusions for the development of future prophylactic and therapeutic viral vaccines.

Is vaccine therapy the future in cancer prevention?

One vaccine designed to prevent cancer by preventing a precursor infection is already in common use, and at least one more is in the latter stages of clinical development. These vaccines are part of a new era of cancer immunoprophylaxis. Several further vaccines are in preclinical and clinical development, targeted at preventing cancer precursor infections, and these should add to our ability to prevent this common human disorder. However, vaccines to prevent cancers not triggered by infection are a more remote prospect, for a variety of reasons.

Attentional bias toward fear-related stimuli: An investigation with nonselected children and adults and children with anxiety disorders

Research investigating anxiety-related attentional bias for emotional information in anxious and nonanxious children has been equivocal with regard to whether a bias for fear-related stimuli is unique to anxious children or is common to children in general. Moreover, recent cognitive theories have proposed that an attentional bias for objectively threatening stimuli may be common to all individuals, with this effect enhanced in anxious individuals. The current study investigated whether an attentional bias toward fear-related pictures could be found in nonselected children (n = 105) and adults (n = 47) and whether a sample of clinically anxious children (n = 23) displayed an attentional bias for fear-related pictures over and above that expected for nonselected children. Participants completed a dot-probe task that employed fear-related, neutral, and pleasant pictures. As expected, both adults and children showed a stronger attentional bias toward fear-related pictures than toward pleasant pictures. Consistent with some findings in the childhood domain, the extent of the attentional bias toward fear-related pictures did not differ significantly between anxious children and nonselected children. However, compared with nonselected children, anxious children showed a stronger attentional bias overall toward affective picture stimuli. (C) 2004 Elsevier Inc. All rights reserved.

Diagnosis of autistic spectrum disorders in Queensland: Variations in practice

Objective: For both paediatricians and child psychiatrists, referrals to assess possible autistic spectrum disorders (ASD) are increasing. This study examines current practices of medical specialists in the assessment of these disorders. Methods: An anonymous, self-report questionnaire was sent to all Queensland paediatricians and child psychiatrists. The survey elicited frequencies of consultation for ASD, diagnostic method, advice provided and perceived adequacy of training for this work. Results: Responses were received from 79 (85%) eligible paediatricians and 26 (58%) eligible child psychiatrists. For one-third of all clinicians, new consultations for possible ASD occurred as often as 2-3 times per week. Most specialists approached the clinical diagnosis of ASD by considering history from different sources and professional assessments. Paediatricians (86%) were more likely than child psychiatrists (62%) to request genetic studies for children with severe autism (P = 0.01). Both general paediatricians and developmental paediatricians perceived level of training for possible ASD consultations was significantly worse than child psychiatrists (P < 0.001 and P = 0.02, respectively), but no difference was found between paediatric groups (P = 0.27). Perceived adequacy of specialist training was not associated with length of experience in clinical practice. Conclusion: Medical practice in Queensland around diagnosis of ASD is characterized by considerable variability. There is still a long way to go if we are to achieve consistency around medical issues of organic diagnosis and practices impacting on health as well as consideration of differential developmental diagnoses. The finding that recently trained paediatricians felt just as unprepared for this work as their older colleagues suggests that the graduate training response to this 'new morbidity' has not been adequate.

Developmental changes in expression of GABA(A) receptor-channels in rat intrinsic cardiac ganglion neurones

The effects of gamma-aminobutyric acid (GABA) on the electrophysiological properties of intracardiac neurones were investigated in the intracardiac ganglion plexus in situ and in dissociated neurones from neonatal, juvenile and adult rat hearts. Focal application of GABA evoked a depolarizing, excitatory response in both intact and dissociated intracardiac ganglion neurones. Under voltage clamp, both GABA and muscimol elicited inward currents at -60 mV in a concentration-dependent manner. The fast, desensitizing currents were mimicked by the GABA(A) receptor agonists muscimol and taurine, and inhibited by the GABA(A) receptor antagonists, bicuculline and picrotoxin. The GABA(A0) antagonist (1,2,5,6-tetrahydropyridin-4-yl)methyl phosphonic acid (TPMPA), had no effect on GABA-induced currents, suggesting that GABA(A) receptor-channels mediate the response. The GABA-evoked current amplitude recorded from dissociated neurones was age dependent whereby the peak current density measured at -100 mV was similar to 20 times higher for intracardiac neurones obtained from neonatal rats (P2-5) compared with adult rats (P45-49). The decrease in GABA sensitivity occurred during the first two postnatal weeks and coincides with maturation of the sympathetic innervation of the rat heart. Immunohistochemical staining using antibodies against GABA demonstrate the presence of GABA in the intracardiac ganglion plexus of the neonatal rat heart. Taken together, these results suggest that GABA and taurine may act as modulators of neurotransmission and cardiac function in the developing mammalian intrinsic cardiac nervous system.