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PubMed2002

The CATH extended protein-family database: providing structural annotations for genome sequences.

An automatic sequence search and analysis protocol (DomainFinder) based on PSI-BLAST and IMPALA, and using conservative thresholds, has been developed for reliably integrating gene sequences from GenBank into their respective structural families within the CATH domain database (http://www.biochem.ucl.ac.uk/bsm/cath_new). DomainFinder assigns a new gene sequence to a CATH homologous superfamily provided that PSI-BLAST identifies a clear relationship to at least one other Protein Data Bank sequence within that superfamily. This has resulted in an expansion of the CATH protein family database (CATH-PFDB v1.6) from 19,563 domain structures to 176,597 domain sequences. A further 50,000 putative homologous relationships can be identified using less stringent cut-offs and these relationships are maintained within neighbour tables in the CATH Oracle database, pending further evidence of their suggested evolutionary relationship. Analysis of the CATH-PFDB has shown that only 15% of the sequence families are close enough to a known structure for reliable homology modeling. IMPALA/PSI-BLAST profiles have been generated for each of the sequence families in the expanded CATH-PFDB and a web server has been provided so that new sequences may be scanned against the profile library and be assigned to a structure and homologous superfamily.

Algorithms↗

PubMed2002

Annotation: Chronic Fatigue Syndrome in children and adolescents.

BACKGROUND: Over the past two decades Chronic Fatigue Syndrome (CFS) of childhood has gained increasing prominence. A number of clinical reports and case-control studies have examined the nature of the disorder, its associations, response to treatment and outcome. METHOD: A review of publications on childhood CFS was undertaken and reference to work on adult CFS made. Most studies on childhood CFS have been on markedly affected children attending specialist pediatric clinics and very little is known about the condition as it presents in the community or to general medical services. RESULTS: The main symptom is fatigue in association with a variety of physical symptoms and with marked and prolonged functional impairment. CFS is commonly reported as being brought on by acute infections. Co-morbid psychiatric (usually mood) disorders are present in at least a half. Personality problems and health attitudes have been described as possible predisposing and maintaining factors. Clinical reports indicate that family work focused on engagement and on a rehabilitation programme (including graded increasing activity and treatment of psychiatric co-morbidity) can help even the more severely impaired children. Recovery may be expected in over two-thirds. CONCLUSIONS: CFS presents as a distinct, markedly impairing disorder of childhood. In its severe form, it is often associated with mood disorders. Further research into milder forms and into the efficacy of different treatment interventions is specially needed.

Adolescent↗

PubMed2002

Annotation: Rett syndrome: recent progress and implications for research and clinical practice.

BACKGROUND: Rett syndrome was first described 40 years ago as a profoundly disabling condition in girls. METHOD: Over the last 20 years' national surveys, neuropathological and neurophysiological research have steadily improved understanding of its character and natural history. RESULTS: In the last two years identification of the causative mutations in the gene methyl CpG binding protein 2 (Xq28) has led to a sudden expansion in knowledge about the underlying developmental disorder, with important implications for clinical practice and new opportunities to develop more effective intervention. CONCLUSIONS: It is now clear that the disorder occurs in males and females and that there is a wide range in severity.

Adolescent↗

PubMed2002

Annotation: the role of prefrontal deficits, low autonomic arousal, and early health factors in the development of antisocial and aggressive behavior in children.

BACKGROUND: This article selectively reviews the biological bases of antisocial and aggressive behavior in children with a focus on low autonomic functioning, prefrontal deficits, and early health factors. RESULTS: Low resting heart rate is thought to be the best-replicated biological correlate of antisocial and aggressive behavior in child and adolescent populations and may reflect reduced noradrenergic functioning and a fearless, stimulation-seeking temperament. Evidence from neuropsychological, neurological, and brain imaging studies converges on the conclusion that prefrontal structural and functional deficits are related to antisocial, aggressive behavior throughout the lifespan. A prefrontal dysfunction theory of antisocial behavior is advanced. This argues that social and executive function demands of late adolescence overload the late developing prefrontal cortex, giving rise to prefrontal dysfunction and a lack of inhibitory control over antisocial, violent behavior that peaks at this age. Birth complications and minor physical anomalies are selectively associated with later violent behavior, especially when combined with adverse psychosocial risk factors for violence. Cigarette smoking during pregnancy may increase the risk for antisocial and violent behavior in later life by disrupting noradrenergic functioning and enhancement of cholinergic receptors that inhibit cardiac functioning. Malnutrition during pregnancy is associated with later antisocial behavior and may be mediated by protein deficiency. CONCLUSIONS: It is argued that early health intervention and prevention studies may provide the most effective way of reversing biological deficits that predispose to antisocial and aggressive behavior in children and adults.

Adolescent↗

PubMed2002

Annotation: attachment disorganisation and psychopathology: new findings in attachment research and their potential implications for developmental psychopathology in childhood.

BACKGROUND: The past 10 years have seen a fruitful line of enquiry building on identification of previously unclassifiable patterns of infant-mother interaction. A critical review of these new findings in attachment theory, highlighting their potential relevance to child psychopathology, is presented. METHOD: Selective literature review relating to disorganised attachment in childhood. RESULTS: Disorganised patterns of attachment have only relatively recently been described. They show characteristic patterns of evolution in development. There is evidence that disorganised attachments are associated with specific forms of distorted parenting, which are distinct from general parental insensitivity and are associated with unresolved loss or trauma in the caregiver. There are also links with aspects of neurodevelopment vulnerability in the child. Attachment disorganisation is a powerful predictor of a range of later social and cognitive difficulties and psychopathology. CONCLUSIONS: The identification of disorganised attachment has greatly increased the potential relevance of attachment theory to general clinical work. However, the concept raises many methodological and theoretical issues. Among issues needing further exploration is the way in which attachment disorganisation relates to children's general mental states and may be affected by cognitive functioning and developmental impairment.

Adolescent↗

PubMed2003

Annotation: The use of psychotropic medications in children: an American view.

BACKGROUND: Psychotropic medications have become an integral component in the treatment of children with mental illnesses. METHODS: Selective reviews of the empirical evidence for the efficacy of psychotropic medications and studies of their use patterns were reviewed. RESULTS: Very strong efficacy for at least the short-term benefits and safety of stimulant medications was found and some good efficacy and safety evidence for the treatment of anxiety and depressive disorders with seratonin reuptake inhibitors (SSRI) was also found. Efficacy for tricyclic antidepressants to treat attention deficit hyperactivity disorder was found but the presence of significant side effects makes them less the drugs of choice. Other medications are presented but with less rigorous evidence. Studies of use found that stimulant medications are extensively prescribed in the US by both psychiatrists and primary care physicians. SSRI are also prescribed extensively but not to the extent of stimulants and are more frequently prescribed by psychiatrists. CONCLUSIONS: There is now good evidence for the efficacy of some psychotropic agents and their use is an integral component in the management of childhood mental illnesses.

Anxiety Disorders↗

PubMed2003

Annotation: The use of psychotropic medications in children: a British view.

BACKGROUND: Prescribing practices relating to the use of psychotropic medication with mentally disordered children have changed significantly in Britain over recent years. METHODS: I conducted a review of the modest body of empirical data available relating to the prescribing practices of child psychiatrists, paediatricians and general practitioners (primary care physicians). The data were obtained primarily from postal questionnaire studies but also from British drug studies and a government-sponsored evaluation of the efficacy of stimulant medication. Postgraduate training guidelines for the three principal clinical disciplines are also discussed. RESULTS: Systematic evaluation of prescribing practices has a relatively short history. All the studies reviewed demonstrated consistent methodological weaknesses, the most important of which was reliance upon retrospective reports of prescribing practices from clinicians with no analysis of actual prescription data. No studies relating to the general use of psychotropic medication by paediatricians were found. Child psychiatrists and general practitioners appear to be using a range of drugs for a range of conditions; however, there was evidence of intra- and interdisciplinary variations in practice. It was also evident from the general practitioner data that drug treatments were frequently used for conditions best managed with behavioural methods (e.g., common sleep problems and enuresis). Government prescription data relating to methylphenidate use in ADHD reveal a dramatic rise over the past ten years. Currently, most child psychiatrists use this treatment compared to approximately half the profession only seven years ago. The use of newer antipsychotic agents as well as the SSRI antidepressants appears to be growing in child psychiatric practice. A majority of clinicians surveyed believed that medication was an important treatment modality but also felt that they were relatively unskilled in the field and requested further training. CONCLUSIONS: Overall, a picture of both a growing and better informed use of psychotropic medication is emerging in Britain despite shortcomings in postgraduate training. Future research needs to evaluate prescribing practice in a more objective manner in order to improve training and also service developments in the field.

Child↗

PubMed2003

Annotation: the neural basis of social impairments in autism: the role of the dorsal medial-frontal cortex and anterior cingulate system.

BACKGROUND: The fundamental social disturbance of autism is characterized, in part, by problems in the acquisition of joint attention skills in the first years of life, followed by impairments in the development of social cognition, as assessed on theory of mind (ToM) measures. Recently, studies have indicated that a system involving the dorsal medial-frontal cortex (DMFC), and the anterior cingulate (AC), may contribute to the development of the tendency to initiate joint attention in infancy. Similarly, research has implicated the DMFC/AC system in ToM performance in typical and atypical individuals. These data suggest it may be useful to consider the functions associated with this system in the developmental psychopathology of autism. METHOD: A review of the studies of the connections between the DMFC/AC system, joint attention and ToM task performance. RESULTS AND CONCLUSIONS: This review raises the hypothesis that the DMFC/AC may be involved in the basic disturbance in social orienting in autism. The DMFAC/AC may also play a role in the capacity to monitor proprioceptive information concerning self-action and integrate this self-related information with exteroceptive perceptual information about the behavior of other people. A disturbance in these functions of the DMFC/ AC may contribute to the atypical development of intersubjectivity, joint attention and social cognition that may impair the lives of people with autism. Thus, impairment in the development of this system may constitute a neural substrate for socio-cognitive deficits in autism.

Attention↗

PubMed2003

Annotation: Hyperlexia: disability or superability?

BACKGROUND: Hyperlexia is the phenomenon of spontaneous and precocious mastery of single-word reading that has been of interest to clinicians and researchers since the beginning of the last century. METHODS: An extensive search of publications on the subject of hyperlexia was undertaken and all available publications were reviewed. RESULTS: The literature can be subdivided into discussions of the following issues: (1) whether hyperlexia is a phenomenon that is characteristic only of specific clinical populations (e.g., children with developmental delays) or whether it can also be observed in the general population; (2) whether hyperlexia is a distinct syndrome comorbid with a number of different disorders or whether it is a part of the spectrum of some other clinical condition(s); (3) whether hyperlexia should be defined through single-word reading superiority with regard to reading comprehension, vocabulary, general intelligence, any combination of the three, or all three characteristics; (4) whether there is a specific neuropsychological profile associated with hyperlexia; (5) whether hyperlexia is characterized by a particular developmental profile; and (6) whether hyperlexia should be viewed as a disability (deficit) or superability (talent). CONCLUSIONS: We interpret the literature as supporting the view that hyperlexia is a superability demonstrated by a very specific group of individuals with developmental disorders (defined through unexpected single-word reading in the context of otherwise suppressed intellectual functioning) rather than as a disability exhibited by a portion of the general population (defined through a discrepancy between levels of single-word reading and comprehension). We simultaneously argue, however, that multifaceted and multi-methodological approaches to studying the phenomenon of hyperlexia, defined within the research framework of understanding single-word reading, are warranted and encouraged.

Adolescent↗

PubMed2001

Annotation: Genetics of reading and spelling disorder.

Recent advances in understanding the genetics of reading and spelling disorder are reviewed and, based on theoretical models of reading development, different related phenotypes such as phonological and orthographic processing are examined. Family and twin studies show a moderate to high familiality and heritability. Segregation analyses suggest a major gene effect, with reduced penetrance in females, as well as a polygenic model. Linkage analyses and an association study have identified possible loci on chromosomes 6 and 15. These results suggest that reading and spelling disorder should be regarded as a complex disorder, strongly influenced by genetic factors. However, the role of environmental factors should also be considered as the clinical implications of the genetic findings in terms of aetiology and intervention still require far more exploration.

Diseases in Twins↗

PubMed1993