A qualitative study of Australian GPs' attitudes and practices in the diagnosis and management of attention-deficit/hyperactivity disorder (ADHD)

Background. The importance of general practice involvement in the care of attention-deficit/hyperactivity disorder (ADHD) is increasing due to the rising numbers of patients who present with the disorder. It has been suggested by consensus bodies that GPs should be identifying and referring patients at the severe end of the ADHD spectrum and managing those with less severe symptoms. However, GPs' views of their role in ADHD care are unknown. Objective. Our aim was to explore the attitudes and practices of Australian GPs towards the diagnosis and management of ADHD. Methods. We conducted a series of focus groups to explore GPs' beliefs regarding the causes of ADHD, their perceived role in ADHD diagnosis and management and their views on the role of behaviour therapies and pharmacotherapies in ADHD management. The subjects were 28 GPs in six focus groups. Results. GPs in this study did not want to be the primary providers of care for patients with ADHD. Participants indicated a preference to refer the patient to medical specialists for diagnosis and treatment of ADHD, and expressed low levels of interest in becoming highly involved in ADHD care. Concerns about overdiagnosis and misdiagnosis of the disorder, diagnostic complexity, time constraints, insufficient education and training about the disorder, and concerns regarding misuse and diversion of stimulant medications were the reasons cited for their lack of willingness. Conclusions. The Australian GPs in this study identify a role for themselves in ADHD care which is largely supportive in nature, and involves close liaison with specialist services.

Cost-effectiveness of dexamphetamine and methylphenidate for the treatment of childhood attention deficit hyperactivity disorder

Objective: To analyze from a health sector perspective the cost-effectiveness of dexamphetamine (DEX) and methylphenidate (MPH) interventions to treat childhood attention deficit hyperactivity disorder (ADHD), compared to current practice. Method: Children eligible for the interventions are those aged between 4 and 17 years in 2000, who had ADHD and were seeking care for emotional or behavioural problems, but were not receiving stimulant medication. To determine health benefit, a meta-analysis of randomized controlled trials was performed for DEX and MPH, and the effect sizes were translated into utility values. An assessment on second stage filter criteria ('equity', 'strength of evidence', 'feasibility' and 'acceptability to stakeholders') is also undertaken to incorporate additional factors that impact on resource allocation decisions. Simulation modelling techniques are used to present a 95% uncertainty interval (UI) around the incremental cost-effectiveness ratio (ICER), which is calculated in cost (in A$) per DALY averted. Results: The ICER for DEX is A$4100/DALY saved (95% UI: negative to A$14 000) and for MPH is A$15 000/DALY saved (95% UI: A$9100-22 000). DEX is more costly than MPH for the government, but much less costly for the patient. Conclusions: MPH and DEX are cost-effective interventions for childhood ADHD. DEX is more cost-effective than MPH, although if MPH were listed at a lower price on the Pharmaceutical Benefits Scheme it would become more cost-effective. Increased uptake of stimulants for ADHD would require policy change. However, the medication of children and wider availability of stimulants may concern parents and the community.

Cost-effectiveness of psychological and pharmacological interventions for generalized anxiety disorder and panic disorder

Objective: To assess from a health sector perspective the incremental cost-effectiveness of interventions for generalized anxiety disorder (cognitive behavioural therapy [CBT] and serotonin and noradrenaline reuptake inhibitors [SNRIs]) and panic disorder (CBT, selective serotonin reuptake inhibitors [SSRIs] and tricyclic antidepressants [TCAs]). Method: The health benefit is measured as a reduction in disability-adjusted life years (DALYs), based on effect size calculations from meta-analyses of randomised controlled trials. An assessment on second stage filters ('equity', 'strength of evidence', 'feasibility' and 'acceptability to stakeholders') is also undertaken to incorporate additional factors that impact on resource allocation decisions. Costs and benefits are calculated for a period of one year for the eligible population (prevalent cases of generalized anxiety disorder/panic disorder identified in the National Survey of Mental Health and Wellbeing, extrapolated to the Australian population in the year 2000 for those aged 18 years and older). Simulation modelling techniques are used to present 95% uncertainty intervals (UI) around the incremental cost-effectiveness ratios (ICERs). Results: Compared to current practice, CBT by a psychologist on a public salary is the most cost-effective intervention for both generalized anxiety disorder (A$6900/DALY saved; 95% UI A$4000 to A$12 000) and panic disorder (A$6800/DALY saved; 95% UI A$2900 to A$15 000). Cognitive behavioural therapy results in a greater total health benefit than the drug interventions for both anxiety disorders, although equity and feasibility concerns for CBT interventions are also greater. Conclusions: Cognitive behavioural therapy is the most effective and cost-effective intervention for generalized anxiety disorder and panic disorder. However, its implementation would require policy change to enable more widespread access to a sufficient number of trained therapists for the treatment of anxiety disorders.

Psychological characteristics of older versus younger persons with a functional gastrointestinal disorder (FGID)

Functional gastrointestinal disorders commonly affect people of all ages, including the elderly. While population-based studies report significant psychological morbidity in people diagnosed with these disorders it is not clear what effect age has in explaining this relationship. We hypothesised that psychological distress would be higher in older versus younger persons with a FGID from the community. A random sample of 4500 subjects were mailed a questionnaire on gastrointestinal symptoms in the past 12 months (response rate = 72%). Of those fulfilling Rome I criteria for a FGID (n = 988) we then classified subjects into older (>60 years) (n =126) versus younger (18-59 years) (n = 862) categories. Psychological variables included anxiety and depression (Delusions Symptom States Inventory) and neuroticism and extroversion (Eysenck Personality Inventory). Quality of life was assessed using the valid SF-12. Anxiety (4.5 vs. 3.1), depression (3.0 vs. 1.8) and neuroticism (5.7 vs. 4.9) were significantly higher in younger versus older subjects with a FGID. While mental functioning (43.1 vs. 48.3) was significantly more impaired in younger versus older subjects, the reverse was found for physical functioning (48.7 vs. 40.8). Younger people with a FGID experience greater

Loss of Ergodicity in the Transition from Annealed to Quenched Disorder in a Finite Kinetic Ising Model

We consider a kinetic Ising model which represents a generic agent-based model for various types of socio-economic systems. We study the case of a finite (and not necessarily large) number of agents N as well as the asymptotic case when the number of agents tends to infinity. The main ingredient are individual decision thresholds which are either fixed over time (corresponding to quenched disorder in the Ising model, leading to nonlinear deterministic dynamics which are generically non-ergodic) or which may change randomly over time (corresponding to annealed disorder, leading to ergodic dynamics). We address the question how increasing the strength of annealed disorder relative to quenched disorder drives the system from non-ergodic behavior to ergodicity. Mathematically rigorous analysis provides an explicit and detailed picture for arbitrary realizations of the quenched initial thresholds, revealing an intriguing ""jumpy"" transition from non-ergodicity with many absorbing sets to ergodicity. For large N we find a critical strength of annealed randomness, above which the system becomes asymptotically ergodic. Our theoretical results suggests how to drive a system from an undesired socio-economic equilibrium (e. g. high level of corruption) to a desirable one (low level of corruption).

Fronto-parietal activation in attention-deficit hyperactivity disorder, combined type: functional magnetic resonance imaging study

A functional magnetic resonance imaging mental rotation paradigm was used to investigate the patterns of activation of fronto-parietal brain areas in male adolescents with attention-deficit hyperactivity disorder, combined type (ADHD-CT) compared with age-, gender-, handedness- and performance IQ-matched healthy controls. The ADHD-CT group had (a) decreased activation of the 'action-attentional' system (including Brodmann's areas (BA) 46, 39,40) and the superior parietal (BA7) and middle frontal (BA10) areas and (b) increased activation of the posterior midline attentional system. These different neuroactivation patterns indicate widespread frontal, striatal and parietal dysfunction in adolescents with ADHD-CT. Declaration of interest None.

Association between dopamine transporter (DATI) genotype, left-sided inattention, and an enhanced response to methylphenidate in attention-deficit hyperactivity disorder

A polymorphism of the dopamine transporter gene (DAT1, 10-repeat) is associated with attention-deficit hyperactivity disorder (ADHD) and has been linked to an enhanced response to methylphenidate (MPH). One aspect of the attention deficit in ADHD includes a subtle inattention to left space, resembling that seen after right cerebral hemisphere damage. Since left-sided inattention in ADHD may resolve when treated with MPH, we asked whether left-sided inattention in ADHD was related to DAT1 genotype and the therapeutic efficacy of MPH. A total of 43 ADHD children and their parents were genotyped for the DAT1 30 variable number of tandem repeats polymorphism. The children performed the Landmark Test, a well-validated measure yielding a spatial attentional asymmetry index ( leftward to rightward attentional bias). Parents rated their child's response to MPH retrospectively using a three-point scale ( no, mediocre or very good response). Additionally, parents used a symptom checklist to rate behavior while on and off medication. A within-family control design determined whether asymmetry indices predicted biased transmission of 10-repeat parental DAT1 alleles and/or response to MPH. It was found that left-sided inattention predicted transmission of the 10-repeat allele from parents to probands and was associated with the severity of ADHD symptomatology. Children rated as achieving a very good response to MPH displayed left-sided inattention, while those rated as achieving a poorer response did not. Our results suggest a subgroup of children with ADHD for whom the 10-repeat DAT1 allele is associated with left-sided inattention. MPH may be most efficacious in this group because it ameliorates a DAT1-mediated hypodopaminergic state.

Tyrosine hydroxylase deficiency: a treatable disorder of brain catecholamine biosynthesis

Tyrosine hydroxylase deficiency is an autosomal recessive disorder resulting from cerebral catecholamine deficiency. Tyrosine hydroxylase deficiency has been reported in fewer than 40 patients worldwide. To recapitulate all available evidence on clinical phenotypes and rational diagnostic and therapeutic approaches for this devastating, but treatable, neurometabolic disorder, we studied 36 patients with tyrosine hydroxylase deficiency and reviewed the literature. Based on the presenting neurological features, tyrosine hydroxylase deficiency can be divided in two phenotypes: an infantile onset, progressive, hypokinetic-rigid syndrome with dystonia (type A), and a complex encephalopathy with neonatal onset (type B). Decreased cerebrospinal fluid concentrations of homovanillic acid and 3-methoxy-4-hydroxyphenylethylene glycol, with normal 5-hydroxyindoleacetic acid cerebrospinal fluid concentrations, are the biochemical hallmark of tyrosine hydroxylase deficiency. The homovanillic acid concentrations and homovanillic acid/5-hydroxyindoleacetic acid ratio in cerebrospinal fluid correlate with the severity of the phenotype. Tyrosine hydroxylase deficiency is almost exclusively caused by missense mutations in the TH gene and its promoter region, suggesting that mutations with more deleterious effects on the protein are incompatible with life. Genotype-phenotype correlations do not exist for the common c.698G > A and c.707T > C mutations. Carriership of at least one promotor mutation, however, apparently predicts type A tyrosine hydroxylase deficiency. Most patients with tyrosine hydroxylase deficiency can be successfully treated with l-dopa.

Functional MR Imaging of visuo-spatial network in Autism Spectrum Disorder

Individuals with Autism Spectrum Disorder (ASD) are generally thought to have impaired attentional and executive function upon which all their cognitive and behaviour functions are based. Mental Rotation is a recognized visuo-spatial task, involving spatial working memory, known to involve activation in the fronto-parietal networks. To elucidate the functioning of fronto-parietal networks in ASD, the aim of this study was to use fMRI techniques with a mental rotation task, to characterize the underlying functional neural system. Sixteen male participants (seven highfunctioning autism or Asperger's syndrome; nine ageand performance IQ-matched controls) underwent fMRI. Participants were presented with 18 baseline and 18 rotation trials, with stimuli rotated 3- dimensionaUy (45°-180°). Data were acquired on a 3- Tesla scanner. The most widely accepted area reported to be involved in processing of visuo-spatial information. Posterior Parietal Cortex, was found to be activated in both groups, however, the ASD group showed decreased activation in cortical and subcortical frontal structures that are highly interconnected, including lateral and medial Brodmann area 6, frontal eye fields, caudate, dorsolateral prefrontal cortex and anterior cingulate. The suggested connectivity between these regions indicates that one or more circuits are impaired as a result of the disorder. In future it is hoped that we are able to identify the possible point of origin of this dysfunction, or indeed if the entire network is dysfunctional.

An examination of movement kinematics in young people with high-functioning autism and Asperger's disorder: Further evidence for a motor planning deficit

This paper examines upper-body movement kinematics in individuals with high-functioning autism (HFA) and Asperger's disorder (AD). In general, the results indicate that HFA is more consistently associated with impaired motoric preparation/initiation than AD. The data further suggest that this quantitative difference in motor impairment is not necessarily underpinned by greater executive dysfunction vulnerability in autism relative to AD. Quantitative motoric dissociation between autism and AD may have down-stream effects on later stages of movement resulting in qualitative differences between these disorder groups, e.g. motor clumsiness in AD versus abnormal posturing in autism. It will be important for future research to map the developmental trajectory of motor abnormalities in these disorder groups.

The Role of SRY Mutations in the Etiology of Gonadal Dysgenesis in Patients with 45,X/46,XY Disorder of Sex Development and Variants

Background: The potential involvement of SRY in abnormal gonadal development in 45,X/46,X,der(Y) patients was proposed following the identification of SRY mutations in a few patients with Turner syndrome (TS). However, its exact etiological role in gonadal dysgenesis in patients with Y chromosome mosaicisms has not yet been clarified. Aims: It was the aim of this study to screen for allelic variation in SRY in a large cohort of patients with disorders of sex development due to chromosomal abnormalities with 45, X/46, X, der(Y) karyotype. Patients: Twenty-seven patients, 14 with TS and 13 with mixed gonadal dysgenesis (MGD), harboring 45, X/46, X, der(Y) karyotypes were selected. Methods: Genomic DNA was extracted from peripheral blood leukocytes of all patients and from gonadal tissue in 4 cases. The SRY coding region was PCR amplified and sequenced. Results: We identified only 1 polymorphism (c.561C -> T) in a 45,X/46,XY MGD patient, which was detected in blood and in gonadal tissue. Conclusion: Our results indicate that mutations in SRY are rare findings in patients with Y chromosome mosaicisms. Therefore, a significant role of mutated SRY in the etiology of gonadal dysgenesis in patients harboring 45, X/46, XY karyotype and variants seems very unlikely. Copyright (C) 2010 S. Karger AG, Basel

Comparison of palmtop-computer-assisted brief cognitive-behavioral treatment to cognitive-behavioral treatment for panic disorder

In the present study, the authors sought to determine whether the efficiency and cost-effectiveness of cognitive-behavioral treatment (CBT) for panic disorder could be improved by adjunctive computer-assisted therapy. Eighteen participants who met Diagnostic and Statistical Manual of Mental Disorders (3rd ed., revised; American Psychiatric Association, 1987) criteria for panic disorder were randomly assigned to a 12-session CBT (CBT12) condition (D. H. Barlow & M. G. Craske, 1989) or to a 4-session computer-assisted CBT (CBT4-CA) condition. Palmtop computers, with a program developed to incorporate basic principles of CBT, were used by CBT4-CA clients whenever they felt anxious or wanted to practice the therapy techniques and were used by all participants as a momentary assessment tool. CBT4-CA clients carried the computer at all times and continued to use it for 8 weeks after termination of therapy. Analyses of clinically significant change showed superiority of CBT12 at posttest on some measures; however, there were no differences at follow-up.

Speech disorder in preschool children exposed to Cantonese and English

Speech disorder in monolingual Cantonese- or English-speaking children has been well described in the literature. There appear to be no reports, however, that describe speech-disordered children who have been exposed to both languages. Here we report on the error patterns of two preschool speech-disordered children who were learning two languages. Both children's first language was Cantonese, but they were also exposed to English through the media and child care. Their disorders were of unknown aetiology. The following questions were asked of the data: (a) Do bilingual children, suspected of having speech problems, make errors in Cantonese and English that reflect delay or disorder when compared with normative data on monolingual speech development in each language? (b) How does the children's speech differ from other bilingual children from the same language learning background? (c) Are the children's speech difficulties apparent in both languages? (d) Is the pattern of errors the same in both languages or do language-specific processes operate? The results bear on theories of acquisition, disorder and bilingualism; they also have clinical implications for speech-language pathologists whose caseloads include bilingual preschool children.