Biomedical subjects
Publications and source records attributed to Eric Taylor.
Attention-deficit hyperactivity disorder (ADHD) is a common disorder affecting children and adults. Many young people treated with stimulants, as well as those in whom ADHD went unrecognised in childhood, need treatment as adults. Stimulants and atomoxetine effectively reduce ADHD symptoms at all ages and should be a standard treatment in general adult psychiatric practice.
BACKGROUND: Fatty acids, in particular omega-3 fatty acids, have been found to affect behavior and cognition both directly and indirectly. Evidence to suggest a link with attention-deficit/hyperactivity disorder (ADHD) derives from three key areas: 1) animal dietary restriction studies observed increased locomotive hyperactivity and reduced cognitive ability in offspring; 2) animal dietary studies indicate alterations in the dopamine pathway; and 3) human studies report reduced plasma omega-3 fatty acids in ADHD subjects. METHODS: We investigated three genes that encode essential enzymes (desaturases) for the metabolism of fatty acids by scanning for genetic association between 45 single nucleotide polymorphisms (SNPs) and ADHD. RESULTS: Our findings suggest a significant association of ADHD with SNP rs498793 (case-control p = .004, odds ratio [OR] 1.6, 95% confidence interval [CI] 1.15-2.23; transmission disequilibrium test [TDT] p = .014, OR 1.69) in the fatty acid desaturase 2 (FADS2) gene. As alcohol is known to decrease the activities of these desaturase enzymes, we also tested for interactions between ADHD subjects' genotypes and maternal use of alcohol during pregnancy. Two SNPs in the fatty acid desaturase 1 (FADS1) gene were nominally associated with ADHD only in the prenatal alcohol-exposed group of children; formal test for interaction was not significant. CONCLUSIONS: These preliminary findings are suggestive of an association between FADS2 and ADHD.
BACKGROUND: In many countries, the majority of children who have Attention Deficit/Hyperactivity Disorder (ADHD) are undiagnosed and there is limited recognition of child mental health problems in primary care. Teachers may be well placed to identify unrecognised children and to facilitate their referral to specialist services. Despite this, there has been limited intervention research addressing teacher identification of ADHD. This study aims to examine whether an educational intervention about ADHD for teachers improves their recognition of children at risk of ADHD. METHOD: A before and after investigation of an educational intervention about ADHD for teachers took place in 6 primary schools (involving 96 class teachers and 2672 pupils). Teacher recognition was compared against a diagnostic algorithm for ADHD caseness that utilised both parent and teacher ratings. Changes in teacher recognition of children with probable ADHD, as well as predictors of recognition, were examined. RESULTS: Following the intervention, there was an increase in the proportion of children regarded by teachers as having probable ADHD. There was also improved agreement between teacher recognition and the diagnostic algorithm. Teacher views that a child had probable ADHD were based on both the severity of symptoms and the impact of these problems on the teacher and the class. CONCLUSIONS: It is feasible to deliver an educational intervention addressing teacher identification of ADHD in routine practice. This was associated with an improvement in the ability of teachers to more accurately identify children at risk of ADHD. The provision of a brief educational intervention for teachers could assist in improving the identification of undiagnosed children with ADHD in the community.
The evolutionary status of attention deficit/hyperactivity disorder (ADHD) is central to assessments of whether modern society has created it, either physically or socially; and is potentially useful in understanding its neurobiological basis and treatment. The high prevalence of ADHD (5-10%) and its association with the seven-repeat allele of DRD4, which is positively selected in evolution, raise the possibility that ADHD increases the reproductive fitness of the individual, and/or the group. However, previous suggestions of evolutionary roles for ADHD have not accounted for its confinement to a substantial minority. Because one of the key features of ADHD is its diversity, and many benefits of population diversity are well recognized (as in immunity), we study the impact of groups' behavioural diversity on their fitness. Diversity occurs along many dimensions, and for simplicity we choose unpredictability (or variability), excess of which is a well-established characteristic of ADHD.Simulations of the Changing Food group task show that unpredictable behaviour by a minority optimizes results for the group. Characteristics of such group exploration tasks are risk-taking, in which costs are borne mainly by the individual; and information-sharing, in which benefits accrue to the entire group. Hence, this work is closely linked to previous studies of evolved altruism.We conclude that even individually impairing combinations of genes, such as ADHD, can carry specific benefits for society, which can be selected for at that level, rather than being merely genetic coincidences with effects confined to the individual. The social benefits conferred by diversity occur both inside and outside the 'normal' range, and these may be distinct. This view has the additional merit of offering explanations for the prevalence, sex and age distribution, severity distribution and heterogeneity of ADHD.
A systematic review of published and unpublished data on the use of long-acting medications in ADHD and hyperkinetic disorder is reported, giving effect sizes and numbers-to-treat for extended-release stimulant preparations and atomoxetine (ATX). A panel of experts from several European countries used the review to make recommendations about the use of these drugs in practice, and conclusions are reported: (1) Long-acting preparations should be available and used; (2) They should not replace short-acting drugs (which will be the initial treatment for many children for reasons of cost and flexibility of dosing). Individual clinical choice is needed. (3) Both ATX and extended-release preparations of stimulants should be available. The choice will depend upon the circumstances, and detailed recommendations are made.
CONTEXT: Attention-deficit/hyperactivity disorder (ADHD) is a common heritable childhood behavioral disorder. Identifying risk factors for ADHD may lead to improved intervention and prevention. The dopamine transporter gene (DAT1) is associated with ADHD in several studies, with an average 1.2 odds ratio and evidence of heterogeneity across data sets. OBJECTIVE: To investigate sources of heterogeneity by refining the DAT1 association using additional markers and investigating gene-environment interaction between DAT1 and maternal use of alcohol and tobacco during pregnancy. DESIGN: Prospective study. SETTING AND PATIENTS: Children with ADHD from child behavior clinics in the southeast of England and in the Taipei area of Taiwan. INTERVENTIONS: Within-family tests of association using 2 repeat polymorphisms in the 3' untranslated region and intron 8 plus additional markers in the English sample. MAIN OUTCOME MEASURES: Transmission ratios of risk alleles from heterozygote parents to affected offspring and comparison of the transmission ratios in high- and low-exposure groups for the environmental variables. RESULTS: A novel association was identified between ADHD, the intron 8 polymorphism, and a specific risk haplotype in both English and Taiwanese samples. The risk haplotype showed significant interactions with maternal use of alcohol during pregnancy. CONCLUSIONS: The identification of a common haplotype in 2 independent populations is an important step toward identifying functionally significant regions of DAT1. Interaction between DAT1 genotypes and maternal use of alcohol during pregnancy suggests that DAT1 moderates the environmental risk and has implications for the prevention of ADHD. Further studies are required to delineate the precise causal risk factor involved in this interaction.
Higher cognitive inhibitory and attention functions have been shown to develop throughout adolescence, presumably concurrent with anatomical brain maturational changes. The relatively scarce developmental functional imaging literature on cognitive control, however, has been inconsistent with respect to the neurofunctional substrates of this cognitive development, finding either increased or decreased executive prefrontal function in the progression from childhood to adulthood. Such inconsistencies may be due to small subject numbers or confounds from age-related performance differences in block design functional MRI (fMRI). In this study, rapid, randomized, mixed-trial event-related fMRI was used to investigate developmental differences of the neural networks mediating a range of motor and cognitive inhibition functions in a sizeable number of adolescents and adults. Functional brain activation was compared between adolescents and adults during three different executive tasks measuring selective motor response inhibition (Go/no-go task), cognitive interference inhibition (Simon task), and attentional set shifting (Switch task). Adults compared with children showed increased brain activation in task-specific frontostriatal networks, including right orbital and mesial prefrontal cortex and caudate during the Go/no-go task, right mesial and inferior prefrontal cortex, parietal lobe, and putamen during the Switch task and left dorsolateral and inferior frontotemporoparietal regions and putamen during the Simon task. Whole-brain regression analyses with age across all subjects showed progressive age-related changes in similar and extended clusters of task-specific frontostriatal, frontotemporal, and frontoparietal networks. The findings suggest progressive maturation of task-specific frontostriatal and frontocortical networks for cognitive control functions in the transition from childhood to mid-adulthood.
OBJECTIVE: A relatively small number of functional imaging studies of attention deficit hyperactivity disorder (ADHD) have shown abnormal prefrontal and striatal brain activation during tasks of motor response inhibition. However, the potential confound of previous medication exposure has not yet been addressed, and no functional imaging study exists to date on medication-naive children and adolescents with ADHD. The aim of this study was to investigate the neural substrates of a range of motor and cognitive inhibitory functions in a relatively large group of children and adolescents with ADHD who had never previously been exposed to medication. METHOD: Nineteen boys with ADHD and 27 healthy age- and IQ-matched boys underwent functional MRI to compare brain activation during performance of tasks that assessed motor response inhibition (go/no go task), cognitive interference inhibition (motor Stroop task), and cognitive flexibility (switch task). RESULTS: Boys with ADHD showed decreased activation in the left rostral mesial frontal cortex during the go/no go task and decreased activation in the bilateral prefrontal and temporal lobes and right parietal lobe during the switch task. No significant group differences were observed during motor Stroop task performance. CONCLUSION: Abnormal brain activation was observed in medication-naive children and adolescents with ADHD during tasks involving motor inhibition and task switching, suggesting that hypoactivation in this patient group is unrelated to long-term stimulant exposure. Furthermore, functional abnormalities are task-specific and extend from frontostriatal to parietal and temporal cortices.
Prudent prescribing of antimicrobial drugs to hospital inpatients may reduce incidences of antimicrobial drug resistance and healthcare-associated infection. We reviewed the literature from January 1980 to November 2003 to identify rigorous evaluations of interventions to improve hospital prescribing of antimicrobial drugs. We identified 66 studies with interpretable data, of which 16 reported 20 microbiologic outcomes: gram-negative resistant bacteria, 10 studies; Clostridium difficile-associated diarrhea, 5 studies; vancomycin-resistant enterococci, 3 studies; and methicillin-resistant Staphylococcus aureus, 2 studies. Four studies provided strong evidence that the intervention changed microbial outcomes with low risk for alternative explanations, 8 studies provided less convincing evidence, and 4 studies provided no evidence. The strongest and most consistent evidence was for C. difficile-associated diarrhea, but we were able to analyze only the immediate impact of interventions because of nonstandardized durations of follow-up. The ability to compare results of studies could be substantially improved by standardizing methods and reporting.
Five independent studies have reported associations between serotonin transporter gene (5-HTT) polymorphisms and attention deficit hyperactivity disorder (ADHD). Four studies found evidence for association between the long-allele of a 44-base pair insertion/deletion polymorphism (5-HTTLPR), one of the studies found association to a variable number tandem repeat within intron 2, another to the T-allele of a single base pair substitution in the 3'-untranslated regions and another reported preferential transmission of a haplotype of the three markers (long-allele/10-repeat-allele/T-allele). One further study found no evidence for these associations. We investigated the association of these three markers in two samples of ADHD patients from the United Kingdom (n = 197) and Taiwan (n = 212), using within-family tests of association. No association was found between any of the three markers in either of the two populations. Although we found some evidence for the preferential transmission of a rare haplotype (long-allele/9-repeat-allele/T-allele; chi2 = 4.5, P = 0.034), we concluded that this most likely occurred by chance factors alone.
The norepinephrine system is known to play a role in attentional and cognitive-energetic mechanisms and is thought to be important in attention deficit hyperactivity disorder (ADHD). Stimulant medications are known to alter the activity of norepinephrine as well as dopamine in the synapse and the highly selective norepinephrine reuptake inhibitor, atomoxetine, is an effective treatment for ADHD symptoms. This study set out to investigate whether common polymorphisms within the norepinephrine transporter gene (NET1) are associated with DSM-IV ADHD combined subtype, using a sample that has previously shown association with genes that affect the synaptic release and uptake of neurotransmitters; DAT1 and SNAP-25. We identified 21 single nucleotide polymorphisms (SNPs) from publicly available databases that had minor allele frequencies > or =5% and span the NET1 genomic region, including those analyzed in previous studies of ADHD. DNA pooling was used to screen for associations using two case pools (n = 180 cases) and four control pools (n = 334 controls). We identified three SNPs that showed suggestive evidence for association using either case-control or within family tests of association, however, none of these were significant after adjustment for the number of markers analyzed. We conclude that none of the markers show significant evidence of association with ADHD although we cannot rule out small genetic effects.
The aim of the study was to clarify the developmental risk for interpersonal relationship problems and ineffective coping strategies associated with hyperactive behaviour in girls in a longitudinal epidemiological design. This was investigated in a follow-up study of girls who were identified by parent and teacher ratings in a large community survey of 6- and 7-year-olds as showing pervasive hyperactivity or conduct problems or the comorbid mixture of both problems or neither problem. They were later investigated, at the age of 14-16 years, in a detailed interview. Childhood hyperactivity was a risk for disrupted relationships in adolescence with peers and the opposite sex, but not parents. Findings were independent of the existence of conduct problems. Hyperactivity was a risk for the use of a wide variety of ineffective coping strategies. On the other hand, conduct problem girls reported applying specific coping strategies, but rated these to be ineffective. It is concluded that early therapeutic interventions targeting the development of social skills and problem-solving skills are required in order to help overcome these problems in later life.
BACKGROUND: While general population studies indicate an increase in the rate of psychiatric disorder in adolescence, little is known about the course of mental health and behaviour problems between childhood and adolescence in young people with severe intellectual disabilities. METHOD: From a sample of 111 children with severe intellectual disability who had been identified from the registers of six special schools at 4-11 years of age, 82 were traced and reassessed 5 years later at the age of 11-17 years. Behaviour problems were assessed by means of parental interviews conducted in the family home and parent and teacher questionnaires. Parental reports of psychiatric diagnoses were checked against health records. RESULTS: With most behaviour problems, including aggression, destructive behaviour and self-injury, there was little difference in rates between the two assessment occasions. However, in spite of this overall pattern of stability, the rates of some behaviour problems, including overactivity, showed significant reductions between childhood and early adolescence. Persistence rates for most behaviour problems appeared comparable to those reported for similar behaviours in general population studies of children. There was no significant difference in the proportion of cases with psychiatric diagnoses between the two assessment occasions, although brief psychotic episodes emerged in three cases in adolescence. CONCLUSIONS: The findings suggest that the prevalence of mental health and behavioural problems in young people with severe learning disabilities remains relatively stable between childhood and adolescence, although some specific behaviour problems diminish. However, a small minority of children may develop severe psychiatric disorders in adolescence.
Most attention deficit hyperactivity disorder (ADHD) research has compared cases with unaffected controls. This has led to many associations, but uncertainties about their specificity to ADHD in contrast with other disorders. We present a selective review of research, comparing ADHD with other disorders in neuropsychological, neurobiological and genetic correlates. So far, a specific pathophysiological pathway has not been identified. ADHD is probably not specifically associated with executive function deficits. It is possible, but not yet established, that ADHD symptoms may be more specifically associated with motivational abnormalities, motor organization and time perception. Recent findings indicating common genetic liabilities of ADHD and other conditions raise questions about diagnostic boundaries. In future research, the delineation of the pathophysiological mechanisms of ADHD needs to match cognitive, imaging and genetic techniques to the challenge of defining more homogenous clinical groups; multi-site collaborative projects are needed.
BACKGROUND: The aim of the study was to clarify the developmental risk associated with hyperactive behaviour in girls in a longitudinal epidemiological design. METHODS: This was investigated in a follow-up study of girls who were identified by parent and teacher ratings in a large community survey of 6- and 7-year-olds as showing pervasive hyperactivity or conduct problems or the comorbid mixture of both problems or neither problem. They were later investigated, at the age of 14 to 16 years, with a detailed self-report interview technique. RESULTS: Hyperactivity was a risk factor for later development, even allowing for the coexistence of conduct problems. Hyperactivity predicted academic problems and interpersonal relationship problems. Relationships with parents, by contrast, were not portrayed to be as problematic as relationships with peers and the opposite sex. Their psychological, social and occupational functioning was objectively rated to be more deviant and their self-report showed them to be more ambivalent about their future. There was a trend for hyperactivity to be self-reported as a risk for the development of continuing symptomatology but neither hyperactivity nor conduct problems were self-reported to be a risk for antisocial behaviour, substance misuse or low self-esteem in adolescence. However, they were at risk for the development of state anxiety. CONCLUSIONS: The results suggested girls' pattern of functioning may differ from that of boys because girls self-report a more pervasive range of social dysfunction than that previously reported in boys.
BACKGROUND: Knowledge of genetic influences, on developmental disorders such as autism spectrum, attention deficit/hyperactivity disorder and learning disabilities, has increased the opportunities for understanding the influences of the early environment. METHODS: This paper provides a selective, narrative review for clinicians of the effects of factors such as exposure to toxins and stresses in utero and in postnatal life; brain injuries and perinatal compromise; neglect, malnutrition and selective food deficiencies. It also considers what is known about the mechanisms through which early adversities operate. RESULTS: Gaps in the research are identified and suggestions made about clinical investigations. Several types of environmental adversity have associations with later disorders that suggest a causal role. The effects are often on a broad range of psychological processes, and are not always quickly reversible. Several adversities often coexist, calling for skilled judgement about priorities in treatment. CONCLUSIONS: Individuals vary considerably in their exposure to adversity and their vulnerability to its effects, and genetic inheritance can influence both.
OBJECTIVE: Patients with attention deficit hyperactivity disorder (ADHD) and a medication history have shown abnormal brain activation in prefrontal and striatal brain regions during cognitive challenge. Previous findings have been confounded, however, by potential long-term effects of stimulant medication exposure and group discrepancies in task performance. The aim of this study was to investigate whether medication-naive adolescents with ADHD would still show abnormal brain activation in prefrontal brain regions during motor response inhibition in a task designed to control for intergroup performance discrepancies. METHOD: Rapid, event-related functional magnetic resonance imaging was used to compare brain activation in 16 medication-naive ADHD adolescents and 21 IQ-, age-, and sex-matched healthy comparison volunteers during a challenging, idiosyncratically adjusted task that required withholding of a triggered motor response. The design, which manipulated task parameters to force each subject to fail on 50% of trials, ensured that subjects worked at the edge of their own inhibitory performance, thereby controlling for intersubject and intergroup performance discrepancies and furthermore allowing for investigation of differences in brain activation related to inhibition and inhibition failure. RESULTS: Medication-naive adolescents with ADHD showed significantly reduced brain activation in the right inferior prefrontal cortex during successful motor response inhibition and in the precuneus and posterior cingulate gyrus during inhibition failure, both of which correlated with behavioral scores of ADHD. CONCLUSIONS: The study shows that abnormal brain activation during inhibitory challenge in ADHD is specific to the disorder, since it persists when medication history and performance discrepancies are excluded.