Meta-analysis of structural imaging findings in Attention-Deficit/Hyperactivity Disorder

Background Although there are many structural neuroimaging studies of attention-deficit/hyperactivity disorder (ADHD) in children, there are inconsistencies across studies and no consensus regarding which brain regions show the most robust area or volumetric reductions relative to control subjects. Our goal was to statistically analyze structural imaging data via a meta-analysis to help resolve these issues. Methods We searched the MEDLINE and PsycINFO databases through January 2005. Studies must have been written in English, used magnetic resonance imaging, and presented the means and standard deviations of regions assessed. Data were extracted by one of the authors and verified independently by another author. Results Analyses were performed using STATA with metan, metabias, and metainf programs. A meta-analysis including all regions across all studies indicated global reductions for ADHD subjects compared with control subjects, standardized mean difference equal to .408, p less than .001. Regions most frequently assessed and showing the largest differences included cerebellar regions, the splenium of the corpus callosum, total and right cerebral volume, and right caudate. Several frontal regions assessed in only two studies also showed large significant differences. Conclusions This meta-analysis provides a quantitative analysis of neuroanatomical abnormalities in ADHD and information that can be used to guide future studies.

Diagnosing adult Attention Deficit Hyperactivity Disorder: Are late onset and subthreshold ciagnoses valid?

Objective Diagnosing attention deficit hyperactivity disorder (ADHD) in adults is difficult when diagnosticians cannot establish an onset before the DSM-IV criterion of age 7 or if the number of symptoms recalled does not achieve DSM’s diagnosis threshold. Method The authors addressed the validity of DSM-IV’s age-at-onset and symptom threshold criteria by comparing four groups of adults: 127 subjects with full ADHD who met all DSM-IV criteria for childhood-onset ADHD, 79 subjects with late-onset ADHD who met all criteria except the age-at-onset criterion, 41 subjects with subthreshold ADHD who did not meet full symptom criteria for ADHD, and 123 subjects without ADHD who did not meet any criteria. The authors hypothesized that subjects with late-onset and subthreshold ADHD would show patterns of psychiatric comorbidity, functional impairment, and familial transmission similar to those seen in subjects with full ADHD. Result Subjects with late-onset and full ADHD had similar patterns of psychiatric comorbidity, functional impairment, and familial transmission. Most children with late onset of ADHD (83%) were younger than 12. Subthreshold ADHD was milder and showed a different pattern of familial transmission than the other forms of ADHD. Conclusions The data about the clinical features of probands and the pattern of transmission of ADHD among relatives found little evidence for the validity of subthreshold ADHD among such subjects, who reported a lifetime history of some symptoms that never met DSM-IV’s threshold for diagnosis. In contrast, the results suggested that late-onset adult ADHD is valid and that DSM-IV’s age-at-onset criterion is too stringent.

Neuropsychological studies of late onset and subthreshold diagnoses of adult Attention-Deficit/Hyperactivity Disorder

Background Diagnosing attention-deficit/hyperactivity disorder (ADHD) in adults is difficult when the diagnostician cannot establish an onset prior to the DSM-IV criterion of age 7 or if the number of symptoms recalled does not achieve the DSM-IV threshold for diagnosis. Because neuropsychological deficits are associated with ADHD, we addressed the validity of the DSM-IV age at onset and symptom threshold criteria by using neuropsychological test scores as external validators. Methods We compared four groups of adults: 1) full ADHD subjects met all DSM-IV criteria for childhood-onset ADHD; 2) late-onset ADHD subjects met all criteria except the age at onset criterion; 3) subthreshold ADHD subjects did not meet full symptom criteria; and 4) non-ADHD subjects did not meet any of the above criteria. Results Late-onset and full ADHD subjects had similar patterns of neuropsychological dysfunction. By comparison, subthreshold ADHD subjects showed few neuropsychological differences with non-ADHD subjects. Conclusions Our results showing similar neuropsychological underpinning in subjects with late-onset ADHD suggest that the DSM-IV age at onset criterion may be too stringent. Our data also suggest that ADHD subjects who failed to ever meet the DSM-IV threshold for diagnosis have a milder form of the disorder.

Susceptibility locus on chromosome 1q23-25 for a schizophrenia subtype resembling deficit schizophrenia identified by latent class analysis

Context: Identifying susceptibility genes for schizophrenia may be complicated by phenotypic heterogeneity, with some evidence suggesting that phenotypic heterogeneity reflects genetic heterogeneity. Objective: To evaluate the heritability and conduct genetic linkage analyses of empirically derived, clinically homogeneous schizophrenia subtypes. Design: Latent class and linkage analysis. Setting: Taiwanese field research centers. Participants: The latent class analysis included 1236 Han Chinese individuals with DSM-IV schizophrenia. These individuals were members of a large affected-sibling-pair sample of schizophrenia (606 ascertained families), original linkage analyses of which detected a maximum logarithm of odds (LOD) of 1.8 (z = 2.88) on chromosome 10q22.3. Main Outcome Measures: Multipoint exponential LOD scores by latent class assignment and parametric heterogeneity LOD scores. Results: Latent class analyses identified 4 classes, with 2 demonstrating familial aggregation. The first (LC2) described a group with severe negative symptoms, disorganization, and pronounced functional impairment, resembling “deficit schizophrenia.” The second (LC3) described a group with minimal functional impairment, mild or absent negative symptoms, and low disorganization. Using the negative/deficit subtype, we detected genome-wide significant linkage to 1q23-25 (LOD = 3.78, empiric genome-wide P = .01). This region was not detected using the DSM-IV schizophrenia diagnosis, but has been strongly implicated in schizophrenia pathogenesis by previous linkage and association studies.Variants in the 1q region may specifically increase risk for a negative/deficit schizophrenia subtype. Alternatively, these results may reflect increased familiality/heritability of the negative class, the presence of multiple 1q schizophrenia risk genes, or a pleiotropic 1q risk locus or loci, with stronger genotype-phenotype correlation with negative/deficit symptoms. Using the second familial latent class, we identified nominally significant linkage to the original 10q peak region. Conclusion: Genetic analyses of heritable, homogeneous phenotypes may improve the power of linkage and association studies of schizophrenia and thus have relevance to the design and analysis of genome-wide association studies.

Adolescence: A useful concept for this millennium

‘Adolescence’ has become increasingly recognised as a nebulous concept. Previous conceptualisations of adolescence have adopted a ‘deficit’ view, regarding teenagers as ‘unfinished’ adults. The deficit view of adolescence is highly problematic in an era where adulthood itself is difficult to define. The terms ‘kidult’ or ‘adultescent’ have emerged to describe adult-age people whose interests and priorities match those of their teenage counterparts. Rather than relying on ‘lock-step’ models of physical, cognitive and social growth put forward by developmental psychology, adolescence can be more usefully defined by looking at the common experiences of people in their teenage years. Common experiences arise at an institutional level; for example, all adolescents are treated as the same by legal and education systems. The transition from primary to secondary schooling is a milestone for all children, exposing them to a new type of educational environment. Shared experiences also arise from generational factors. Today’s adolescents belong to the millennial generation, characterised by technological competence, global perspectives, high susceptibility to media influence, individualisation and rapid interactions. This generation focuses on teamwork, achievement, modesty and good conduct, and has great potential for significant collective accomplishments. These generational factors challenge educators to provide relevant learning experiences for today’s students. Many classrooms still utilise textbook-based pedagogy more suited to previous generations, resulting in disengagement among millennial students. Curriculum content must also be tailored to generational needs. The rapid pace of change, as well as the fluidity of identity created by dissolving geographical and vocational boundaries, mean that the millennial generation will need more than a fixed set of skills and knowledge to enter adulthood. Teachers must enable their students to think like ‘expert novices’, adept at assimilating new concepts in depth and prepared to engage in lifelong learning.

Be careful what you ask for : how inquiry strategy influences readiness mode

Much has been written about affecting change in the workplace, including how to help employees prepare for the process. However, little is known about how participation influences employees' emotions and attitudes at the start of an intervention. By qualitatively analyzing conversations that were triggered by an organizational change effort, we explored how different inquiry strategies influence readiness for change. We examined four inquiry strategies by combining strength or deficit frames with individual or organizational focus. Distinctive conversational patterns emerged within each strategy, which we believe influence peoples' change readiness. In this article we present four readiness modes to describe these patterns and conclude with implications for managers who seek to shape their change efforts more effectively.

Predatory police : the roles of ethics and networks as mediating factors

The institution the police force has been established to protect citizens and their property from harm and predatory opportunism. However, there have been occasions when the very people assigned to protect become part of the predatory force against society. Predatory policing occurs when the police use their powers to extort money in the form of bribes. While, the concept is receiving attention in Europe but there have not been any direct studies in Australia. To overcome this research deficit and determine the extent, if any, of predatory policing in Australia data is interrogated from four police corruption inquiries in the Australian states of Queensland, New South Wales, Victoria and Western Australia. In addition, it examines the role of the type of networks used by corrupt police officers. The synthesis and application of public corruption and network literatures to the predatory policing domain provides new and relevant insights to assist those responsible for the administration of our institutions of justice. The paper concludes with a framework, drawn from the first stage of the project, to assist in the conceptualisation and monitoring of this public problem.

Biochemical characterization of Aprataxin, the protein deficient in Ataxia with Oculomotor Apraxia type 1

Neurodegenerative disorders are heterogenous in nature and include a range of ataxias with oculomotor apraxia, which are characterised by a wide variety of neurological and ophthalmological features. This family includes recessive and dominant disorders. A subfamily of autosomal recessive cerebellar ataxias are characterised by defects in the cellular response to DNA damage. These include the well characterised disorders Ataxia-Telangiectasia (A-T) and Ataxia-Telangiectasia Like Disorder (A-TLD) as well as the recently identified diseases Spinocerebellar ataxia with axonal neuropathy Type 1 (SCAN1), Ataxia with Oculomotor Apraxia Type 2 (AOA2), as well as the subject of this thesis, Ataxia with Oculomotor Apraxia Type 1 (AOA1). AOA1 is caused by mutations in the APTX gene, which is located at chromosomal locus 9p13. This gene codes for the 342 amino acid protein Aprataxin. Mutations in APTX cause destabilization of Aprataxin, thus AOA1 is a result of Aprataxin deficiency. Aprataxin has three functional domains, an N-terminal Forkhead Associated (FHA) phosphoprotein interaction domain, a central Histidine Triad (HIT) nucleotide hydrolase domain and a C-terminal C2H2 zinc finger. Aprataxins FHA domain has homology to FHA domain of the DNA repair protein 5’ polynucleotide kinase 3’ phosphatase (PNKP). PNKP interacts with a range of DNA repair proteins via its FHA domain and plays a critical role in processing damaged DNA termini. The presence of this domain with a nucleotide hydrolase domain and a DNA binding motif implicated that Aprataxin may be involved in DNA repair and that AOA1 may be caused by a DNA repair deficit. This was substantiated by the interaction of Aprataxin with proteins involved in the repair of both single and double strand DNA breaks (XRay Cross-Complementing 1, XRCC4 and Poly-ADP Ribose Polymerase-1) and the hypersensitivity of AOA1 patient cell lines to single and double strand break inducing agents. At the commencement of this study little was known about the in vitro and in vivo properties of Aprataxin. Initially this study focused on generation of recombinant Aprataxin proteins to facilitate examination of the in vitro properties of Aprataxin. Using recombinant Aprataxin proteins I found that Aprataxin binds to double stranded DNA. Consistent with a role for Aprataxin as a DNA repair enzyme, this binding is not sequence specific. I also report that the HIT domain of Aprataxin hydrolyses adenosine derivatives and interestingly found that this activity is competitively inhibited by DNA. This provided initial evidence that DNA binds to the HIT domain of Aprataxin. The interaction of DNA with the nucleotide hydrolase domain of Aprataxin provided initial evidence that Aprataxin may be a DNA-processing factor. Following these studies, Aprataxin was found to hydrolyse 5’adenylated DNA, which can be generated by unscheduled ligation at DNA breaks with non-standard termini. I found that cell extracts from AOA1 patients do not have DNA-adenylate hydrolase activity indicating that Aprataxin is the only DNA-adenylate hydrolase in mammalian cells. I further characterised this activity by examining the contribution of the zinc finger and FHA domains to DNA-adenylate hydrolysis by the HIT domain. I found that deletion of the zinc finger ablated the activity of the HIT domain against adenylated DNA, indicating that the zinc finger may be required for the formation of a stable enzyme-substrate complex. Deletion of the FHA domain stimulated DNA-adenylate hydrolysis, which indicated that the activity of the HIT domain may be regulated by the FHA domain. Given that the FHA domain is involved in protein-protein interactions I propose that the activity of Aprataxins HIT domain may be regulated by proteins which interact with its FHA domain. We examined this possibility by measuring the DNA-adenylate hydrolase activity of extracts from cells deficient for the Aprataxin-interacting DNA repair proteins XRCC1 and PARP-1. XRCC1 deficiency did not affect Aprataxin activity but I found that Aprataxin is destabilized in the absence of PARP-1, resulting in a deficiency of DNA-adenylate hydrolase activity in PARP-1 knockout cells. This implies a critical role for PARP-1 in the stabilization of Aprataxin. Conversely I found that PARP-1 is destabilized in the absence of Aprataxin. PARP-1 is a central player in a number of DNA repair mechanisms and this implies that not only do AOA1 cells lack Aprataxin, they may also have defects in PARP-1 dependant cellular functions. Based on this I identified a defect in a PARP-1 dependant DNA repair mechanism in AOA1 cells. Additionally, I identified elevated levels of oxidized DNA in AOA1 cells, which is indicative of a defect in Base Excision Repair (BER). I attribute this to the reduced level of the BER protein Apurinic Endonuclease 1 (APE1) I identified in Aprataxin deficient cells. This study has identified and characterised multiple DNA repair defects in AOA1 cells, indicating that Aprataxin deficiency has far-reaching cellular consequences. Consistent with the literature, I show that Aprataxin is a nuclear protein with nucleoplasmic and nucleolar distribution. Previous studies have shown that Aprataxin interacts with the nucleolar rRNA processing factor nucleolin and that AOA1 cells appear to have a mild defect in rRNA synthesis. Given the nucleolar localization of Aprataxin I examined the protein-protein interactions of Aprataxin and found that Aprataxin interacts with a number of rRNA transcription and processing factors. Based on this and the nucleolar localization of Aprataxin I proposed that Aprataxin may have an alternative role in the nucleolus. I therefore examined the transcriptional activity of Aprataxin deficient cells using nucleotide analogue incorporation. I found that AOA1 cells do not display a defect in basal levels of RNA synthesis, however they display defective transcriptional responses to DNA damage. In summary, this thesis demonstrates that Aprataxin is a DNA repair enzyme responsible for the repair of adenylated DNA termini and that it is required for stabilization of at least two other DNA repair proteins. Thus not only do AOA1 cells have no Aprataxin protein or activity, they have additional deficiencies in PolyADP Ribose Polymerase-1 and Apurinic Endonuclease 1 dependant DNA repair mechanisms. I additionally demonstrate DNA-damage inducible transcriptional defects in AOA1 cells, indicating that Aprataxin deficiency confers a broad range of cellular defects and highlighting the complexity of the cellular response to DNA damage and the multiple defects which result from Aprataxin deficiency. My detailed characterization of the cellular consequences of Aprataxin deficiency provides an important contribution to our understanding of interlinking DNA repair processes.

Expressed emotion as predictor of relapse in patients with comorbid psychoses and substance use disorder

Objective: Expressed emotion (EE) and substance use disorder predict relapse in psychosis, but there is little research on EE in comorbid samples. The current study addressed this issue. Method: Sixty inpatients with a DSM-IV psychosis and substance use disorder were recruited and underwent diagnostic and substance use assessment. Key relatives were administered the Camberwell Family Interview. Results: Patients were assessed on the initial symptoms and recent substance use, and 58 completed the assessment over the following 9 months. High EE was observed in 62% of households. Expressed emotion was the strongest predictor of relapse during follow up and its predictive effect remained in participants with early psychosis. A multivariate prediction of a shorter time to relapse entered EE, substance use during follow up Q1 and (surprisingly) an absence of childhood attention deficit hyperactivity disorder. Conclusions: Since high EE is a common and important risk factor for people with comorbid psychosis and substance misuse, approaches to address it should be considered by treating clinicians.

The logic of ADHD : a brief review of fallacious reasoning

This paper has two central purposes: the first is to survey some of the more important examples of fallacious argument, and the second is to examine the frequent use of these fallacies in support of the psychological construct: Attention Deficit Hyperactivity Disorder (ADHD). The paper divides 12 familiar fallacies into three different categories—material, psychological and logical—and contends that advocates of ADHD often seem to employ these fallacies to support their position. It is suggested that all researchers, whether into ADHD or otherwise, need to pay much closer attention to the construction of their arguments if they are not to make truth claims unsupported by satisfactory evidence, form or logic.

The ADHD debate and the philosophy of truth

There is ongoing and wide-ranging dispute over the proliferation of childhood behaviour disorders. In particular, the veracity of the category Attention Deficit Hyperactivity Disorder (ADHD), has been the subject of considerable scepticism. With no end to the debate in sight, it will be argued here that the problem might effectively be approached, not by addressing the specific features of ADHD itself, but rather by a philosophical analysis of one of the terms around which this entire problem revolves: that is, the notion of truth. If we state: “It is true that ADHD is a real disorder”, what exactly do we mean? Do we mean that it is an objective fact of nature? Do we mean that it fits seamlessly with other sets of ideas and explanations? Or do we simply mean that it works as an idea in a practical sense? This paper will examine the relationship between some of the dominant models of truth, and the assertions made by those in the field of ADHD. Specifically, the paper will contrast the claim that ADHD is a real disorder, with the claim that ADHD is a product of social governance. The intention is, first, to place some significant qualifications upon the validity of the truth-claims made by ADHD advocates, and second, to re-emphasise the potential and promise of philosophical investigation in providing productive new ways of thinking about some obstinate and seemingly intractable educational problems.

Pathologising difference, governing personality

Recent research has stressed the integral part played by teachers in both preliminary diagnosis and ongoing treatment of a range of conduct and personality disorders. Teachers are not only required to be aware of a variety of new categories of difference (Attention Deficit Disorder, Selective Mutism, Borderline Personality Disorder, Antisocial Personality Disorder, to name but a few), but are also now lauded for extending the role of education into new areas of social management. This paper will take issue with this understanding on two counts: first, teachers have always sought to mould the personalities of students, and the pathologisation of specific forms of conduct is simply a new tactic within a very old and familiar strategy. Second, schools do not simply discover disorders such as ADD as objective facts of nature. Rather, they are part of the process through which such differences are created, and by which individuals can be more effectively governed.

A disordered approach

It seems a new behaviour disorder is identified every week. Forms of conduct once simply regarded as part of the human condition, are rapidly being reinterpreted as types of mental illness. Individuals are no longer simply quiet or shy, they are reclassified as suffering from Generalised Social Phobia, or Selective Mutism, or Avoidant Personality Disorder. Others are no longer simply unpopular or obnoxious, they are reclassified as Borderline Personality Disorder, or Antisocial Personality Disorder. Still more are no longer lively or boisterous, they have Attention Deficit Hyperactivity Disorder, or Conduct Disorder, or Oppositional Defiance Disorder.

ADHD : a case study in fallacy

This paper has two central purposes: the first is to survey some of the more important examples of fallacious argument, and the second is to examine the frequent use of these fallacies in support of the psychological construct: Attention Deficit Hyperactivity Disorder (ADHD). The paper divides twelve familiar fallacies into three different categories—material, psychological and logical—and contends that advocates of ADHD often seem to employ these fallacies to support their position. It is suggested that all researchers, whether into ADHD or otherwise, need to pay much closer attention to the construction of their arguments if they are not to make truth claims unsupported by satisfactory evidence, form or logic.

Using resilience to reconceptualise child protection workforce capacity

Current approaches to managing and supporting staff and addressing turnover in child protection predominantly rely on deficit-based models that focus on limitations, shortcomings, and psychopathology. This article explores an alternative approach, drawing on models of resilience, which is an emerging field linked to trauma and adversity. To date, the concept of resilience has seen limited application to staff and employment issues. In child protection, staff typically face a range of adverse and traumatic experiences that have flow-on implications, creating difficulties for staff recruitment and retention and reduced service quality. This article commences with discussion of the multifactorial influences of the troubled state of contemporary child protection systems on staffing problems. Links between these and difficulties with the predominant deficit models are then considered. The article concludes with a discussion of the relevance and utility of resilience models in developing alternative approaches to child protection staffing issues.