Alex J Richardson

University of Oxford | OX · Department of Physiology, Anatomy and Genetics

Sleep problems in children are associated with poor health, behavioural and cognitive problems, as are deficiencies of long-chain omega-3 fatty acids such as docosahexaenoic acid. Theory and some evidence support a role for these fatty acids in sleep regulation, but this issue has received little formal investigation. We examined associations betwe...

Omega-3 long-chain polyunsaturated fatty acids (LC-PUFA), especially DHA (docosahexaenonic acid) are essential for brain development and physical health. Low blood Omega-3 LC-PUFA have been reported in children with ADHD and related behavior/learning difficulties, as have benefits from dietary supplementation. Little is known, however, about blood...

Background: Omega-3 fatty acids are dietary essentials, and the current low intakes in most modern developed countries are believed to contribute to a wide variety of physical and mental health problems. Evidence from clinical trials indicates that dietary supplementation with long-chain omega-3 may improve child behavior and learning, although mo...

Omega-3 fatty acids are dietary essentials, and are critical to brain development and function. Increasing evidence suggests that a relative lack of omega-3 may contribute to many psychiatric and neurodevelopmental disorders. This review focuses on the possible role of omega-3 in attention-deficit/hyperactivity disorder (ADHD) and related childhood...

Increasing evidence suggests that a low dietary intake of the n -3 long-chain PUFA EPA and DHA may contribute not only to the risks for various physical illnesses (particularly cardiovascular and immune system disorders), but also to many disorders of mental health and performance ¹ , ² . From their recent comprehensive review of the evidence for t...

Background Omega-3 fatty acids are central to brain-development of children. Evidence from clinical trials and systematic reviews demonstrates the potential of long-chain Omega-3 supplementation for learning and behavior. However, findings are inconclusive and in need of robust replication studies since such work is lacking. Objectives Replication...

CONSORT checklist. (DOCX)

Prediction of learning and behaviour from DHA change. (DOCX)

Multivariate analyses. (DOCX)

Further details on recruitment. (DOCX)

Blood fatty acid data- methods. (DOCX)

Protocol amendment change of capsule shell. (DOCX)

Randomization technical details. (DOCX)

Does dietary intake of omega-3 DHA influence children's sleep? Sleep problems affecting 40% of UK schoolchildren aged 7–9 years were reported in a recent University of Oxford study and lower blood concentrations of omega-3 DHA predicted more serious sleep problems in these otherwise healthy, normal children. In a randomised controlled trial, dietar...

Blood concentrations of long-chain omega-3 fatty acids in UK children are low, and associated with poor cognitive performance and behaviour, according to a recent study conducted at the University of Oxford.In a randomised controlled trial, dietary supplementation with the long-chain omega-3 DHA (docosahexaenoic acid) significantly improved reading...

Methods for capillary whole blood fatty acid analysis. (DOCX)

Further information on those for whom blood data were available. (DOCX)

Mean levels of Conners’ subscales* in overall sample. (DOCX)

Blood fatty acid levels by pupils’ gender, age, and free school meal entitlement. (DOCX)

Outcome variables (Comparison between pupils with and without blood data). (DOCX)

Demographic variables and outcome variables. (DOCX)

Study protocol. (DOC)

CONSORT checklist. (DOC)

Dyslexia (or reading disability) and specific language impairment (or SLI) are common childhood disorders that show considerable co-morbidity and diagnostic overlaps and have been suggested to share some genetic aetiology. Recently, genetic risk variants have been identified for SLI and dyslexia enabling the direct evaluation of possible shared gen...

Six independent studies have identified linkage to chromosome 18 for developmental dyslexia or general reading ability. Until now, no candidate genes have been identified to explain this linkage. Here, we set out to identify the gene(s) conferring susceptibility by a two stage strategy of linkage and association analysis. Linkage analysis: 264 UK f...

Approximately 90% of humans are right-handed. Handedness is a heritable trait, yet the genetic basis is not well understood. Here we report a genome-wide association study for a quantitative measure of relative hand skill in individuals with dyslexia [reading disability (RD)]. The most highly associated marker, rs11855415 (P = 4.7 × 10−7), is locat...

Bell, G.; Bueno, Allain; Cunnane, S.; Clough, P.; Emmett, P.; Galli, C.; Golding, J.; Harbige, L.; Hibbeln, J.R.; Kirby, A.; Lands, W.E.M.; LeFevre, D.; Lister, R.; Oppenheimer, S.; Rayman, M.; Richardson, A.; von Schacky, C.; Sinclair, A.; Stein, J.; Sullivan, P. and Winkler, J. (2010) Abstract On 2 July 2009, the EFSA Panel on Dietetic products,...

Bipolar disorder is a complex psychiatric disorder and is amongst the top thirty causes of worldwide disability. Mood stabilisers are the primary pharmacological intervention, both in the treatment of acute episodes and in prophylaxis. There is, however, mounting evidence that dietary supplementation with omega-3 fatty acids may be beneficial in ps...

Increasing evidence suggests that dietary deficiencies of omega-3 fatty acids can contribute to many common disorders of behaviour and learning, including Attention-Deficit Hyperactivity Disorder (ADHD), dyslexia, dyspraxia and autism. The highly unsaturated omega-3 fatty acids found in fish oils (EPA and DHA) are absolutely essential for brain dev...

Left-right asymmetrical brain function underlies much of human cognition, behavior and emotion. Abnormalities of cerebral asymmetry are associated with schizophrenia and other neuropsychiatric disorders. The molecular, developmental and evolutionary origins of human brain asymmetry are unknown. We found significant association of a haplotype upstre...

The niacin skin test reflects a flush and oedema owing to the production of prostaglandin D2 from arachidonic acid. A diminished response may indicate abnormalities in the phospholipid metabolism, which has been shown in schizophrenia. There is evidence that dyslexia might also involve phospholipid abnormalities, therefore we examined the skin resp...

The aim of the study was to examine the association of arachidonic acid-related signal transduction with cerebral metabolism in patients with schizophrenia who have violently and dangerously offended while psychotic. Cerebral 31-phosphorus magnetic resonance spectroscopy was carried out in 11 male patients with schizophrenia who had violently offen...

Increasing evidence implicates functional deficiencies or imbalances of omega-3 and omega-6 fatty acids in dyslexia. The associations between literacy skills and omega-3 and omega-6 fatty acid status were examined. 32 dyslexics and 20 controls completed standardised tests of reading and spelling and gave venous blood samples for analysis of the pol...

To determine if the available data support the use of omega-3 essential fatty acids (EFA) for clinical use in the prevention and/or treatment of psychiatric disorders. The authors of this article were invited participants in the Omega-3 Fatty Acids Subcommittee, assembled by the Committee on Research on Psychiatric Treatments of the American Psychi...

The DYX2 locus on chromosome 6p22.2 is the most replicated region of linkage to developmental dyslexia (DD). Two candidate genes within this region have recently been implicated in the disorder: KIAA0319 and DCDC2. Variants within DCDC2 have shown association with DD in a US and a German sample. However, when we genotyped these specific variants in...

Dyslexia is one of the most prevalent childhood cognitive disorders, affecting ∼5% of school-age children. We have recently identified a risk haplotype associated with dyslexia on chromosome 6p22.2 which spans the TTRAP gene and portions of THEM2 and KIAA0319. Here we show that in the presence of the risk haplotype, the expression of the KIAA0319 g...

Developmental coordination disorder (DCD) affects approximately 5% of school-aged children. In addition to the core deficits in motor function, this condition is associated commonly with difficulties in learning, behavior, and psychosocial adjustment that persist into adulthood. Mounting evidence suggests that a relative lack of certain polyunsatur...

A cohort of patients with first-episode schizophrenia was dichotomised into two age- and sex-matched groups of clinical syndromes, the active and withdrawn, and underwent high-resolution three-dimensional magnetic resonance imaging at baseline and 8 months later. A cohort of age- and sex-matched normal controls was also imaged at the same time inte...

Both omega-3 and omega-6 long-chain PUFA (LC-PUFA) are crucial to brain development and function, but omega-3 LC-PUFA in particular are often lacking in modern diets in developed countries. Increasing evidence, reviewed here, indicates that LC-PUFA deficiencies or imbalances are associated with childhood developmental and psychiatric disorders incl...

Several quantitative trait loci (QTLs) that influence developmental dyslexia (reading disability [RD]) have been mapped to chromosome regions by linkage analysis. The most consistently replicated area of linkage is on chromosome 6p23-21.3. We used association analysis in 223 siblings from the United Kingdom to identify an underlying QTL on 6p22.2....

Developmental dyslexia is diagnosed as a specific impairment in reading ability, despite adequate intelligence and educational opportunity,1 that affects approximately 5% of schoolchildren.2 Much evidence has been accumulated from twin and family based studies to indicate that dyslexia can have a hereditary basis, but that the genetic aetiology is...

This study explores the relationship between attentional processing mediated by visual magnocellular (MC) processing and reading ability. Reading ability in a group of primary school children was compared to performance on a visual cued coherent motion detection task. The results showed that a brief spatial cue was more effective in drawing attenti...

This is the protocol for a review and there is no abstract. The objectives are as follows: To review the efficacy of omega-3 fatty acids as an adjunctive treatment for bipolar disorder. To investigate the effects of pure preparations of specific omega-3 fatty acids such as Alpha-linolenic acid (ALA), Eicosapentaenoic acid (EPA) and Docosahexaenoic...

Developmental dyslexia is associated with deficits in the processing of visual motion stimuli, and some evidence suggests that these motion processing deficits are related to various reading subskills deficits. However, little is known about the mechanisms underlying such associations. This study lays a richer groundwork for exploration of such mec...

Considerable clinical and experimental evidence now supports the idea that deficiencies or imbalances in certain highly unsaturated fatty acids may contribute to a range of common developmental disorders including ADHD, dyslexia, dyspraxia and autistic spectrum disorders (ASD). Definitive evidence of a causal contribution, however, can only come fr...

There is biochemical evidence to suggest that membrane phospholipid metabolism may be impaired in some patients with schizophrenia. The aim of this study was to test the hypothesis that patients with schizophrenia who have violently offended while psychotic suffer from changes in cerebral phospholipid metabolism. Cerebral 31-phosphorus magnetic res...

Reduced omega-3 and omega-6 fatty acids in red blood cell (RBC) membranes are often found in patients with schizophrenia. Here we investigated whether membrane concentrations of these fatty acids might vary as a function of schizotypal traits in non-psychotic individuals. Twenty-five healthy adults completed the O-LIFE schizotypal trait inventory a...

Omega-3 and omega-6 fatty acids are absolutely essential for human life and health, but they must be provided by our diet. They play particularly key roles in brain development and function. Various physical signs are associated with deficiencies in these essential fatty acids. These include excessive thirst, frequent urination, rough, dry or scal...

Recent research has provided evidence for a genetically mediated association between language or reading-related cognitive deficits and impaired motor coordination. Other studies have identified relationships between lateralization of hand skill and cognitive abilities. With a large sample, the authors aimed to investigate genetic relationships bet...

Schizophrenia and non-right-handedness are moderately associated, and both traits are often accompanied by abnormalities of asymmetrical brain morphology or function. We have found linkage previously of chromosome 2p12-q11 to a quantitative measure of handedness, and we have also found linkage of schizophrenia/schizoaffective disorder to this same...

There is mounting evidence that functional deficiencies or imbalances in certain highly unsaturated fatty acids (HUFA) of the omega-3 and omega-6 series may contribute to a wide range of developmental and psychiatric conditions, including dyslexia, dyspraxia, attention deficit hyperactivity disorder (ADHD), autism, depression, bipolar disorder and...

Replication of linkage results for complex traits has been exceedingly difficult, owing in part to the inability to measure the precise underlying phenotype, small sample sizes, genetic heterogeneity, and statistical methods employed in analysis. Often, in any particular study, multiple correlated traits have been collected, yet these have been ana...

Numerous studies have shown that, as a group, children or adults with developmental dyslexia perceive isolated syllables or words abnormally. Continuous speech containing reduced acoustic information also might prove perceptually difficult to such listeners. They might, however, exploit the intact syntactic and semantic features present in whole ut...

Developmental dyslexia is a complex syndrome showing overlaps and associations not only with many other developmental disorders of childhood such as dyspraxia, ADHD and autistic spectrum disorders, but also with certain adult psychiatric conditions – notably anxiety, depression and some conditions within the schizophrenia spectrum (Richardson and R...

Recent evidence has suggested cerebellar anomalies in developmental dyslexia. Therefore, we investigated cerebellar morphology in subjects with documented reading disabilities. We obtained T1-weighted magnetic resonance images in the coronal and sagittal planes from 11 males with prior histories of developmental dyslexia, and nine similarly-aged ma...

Genomewide quantitative-trait locus (QTL) linkage analysis was performed using a continuous measure of relative hand skill (PegQ) in a sample of 195 reading-disabled sibling pairs from the United Kingdom. This was the first genomewide screen for any measure related to handedness. The mean PegQ in the sample was equivalent to that of normative data,...

Developmental dyslexics reportedly discriminate auditory frequency poorly. A recent study found no such deficit. Unlike its predecessors, however, it employed multiple exposures per trial to the standard stimulus. To investigate whether this affects frequency discrimination in dyslexics, a traditional two-interval same-different paradigm (2I_1A_X)...

(1) The authors tested the prediction that relative deficiencies in highly unsaturated fatty acids (HUFAs) may underlie some of the behavioral and learning problems associated with attention-deficit/hyperactivity disorder (ADHD) by studying the effects of HUFA supplementation on ADHD-related symptoms in children with specific learning difficulties...

Developmental dyslexia is defined as a specific and significant impairment in reading ability that cannot be explained by deficits in intelligence, learning opportunity, motivation or sensory acuity. It is one of the most frequently diagnosed disorders in childhood, representing a major educational and social problem. It is well established that dy...

(1) It is possible to investigate aspects of phospholipid-related signal transduction in humans noninvasively using the niacin skin flush test. (2) Patients with schizophrenia have previously been reported to show a reduced flushing response. (3) The aim of this study was to devise a comprehensive index of cutaneous response to the niacin test, inc...

A 6-month randomized, placebo-controlled pilot study of the ethyl-ester of eicosapentaenoic acid (ethyl-EPA) was carried out in seven in-patients with advanced (stage III) Huntington's disease (three on ethyl-EPA, four on placebo; no significant difference in age or sex between the groups). After 6 months all the patients treated with ethyl-EPA imp...

Dyslexia alone affects at least 5% of the general population in a severe form, as does ADHD, although estimates rise when milder forms are included. Dyspraxia remains less well-known, but prevalence appears to be similar. There is considerable overlap between dyslexia, dyspraxia and ADHD as well as autistic spectrum disorders, and each of these syn...

Recent evidence has suggested cerebellar anomalies in developmental dyslexia. Therefore, we investigated cerebellar morphology in subjects with documented reading disabilities. We obtained T1-weighted magnetic resonance images in the coronal and sagittal planes from 11 males with prior histories of developmental dyslexia, and nine similarly-aged ma...

Summary 1. Dyspraxia or developmental coordination disorder (DCD) shows substantial overlap with other developmental and psychiatric conditions both within individuals and within families – notably dyslexia, ADHD and autistic spectrum disorders, but also mood disorders and schizophrenia spectrum disorders. This indicates some common predisposing fa...

1.Abnormal neuronal membrane phospholipid metabolism is increasingly recognized as being of central importance to a number of neuropsychiatric disorders. Currently, two important indices of membrane phospholipid metabolism tend to be measured: the ratio of the areas of the phosphomonoester (PME) and phosphodiester (PDE) peaks from in vivo cerebral...

The n-3 essential fatty acid eicosapentaenoic acid (EPA) was added to the conventional antidepressant treatment of a treatment-resistant severely depressed and suicidal male patient with a seven-year history of unremitting depressive symptoms. The niacin skin flush test and cerebral magnetic resonance scanning were carried out at baseline and nine...

The aim of this study was to confirm a recent report that the non-invasive niacin skin flush test can be used to demonstrate impaired arachidonic acid-related signal transduction in schizophrenia. The response to topical aqueous methyl nicotinate solution was recorded at five-minute intervals over 20 minutes in 21 patients with schizophrenia, and i...

Post-mortem studies by Galaburda and colleagues on the brains of developmental dyslexics found characteristic neuronal abnormalities: ectopias, microgyria, and fewer large-soma cells in sensory thalamus. An association between dyslexia and immune dysfunction has also been proposed. We describe a mechanism which may explain these observations. Plate...

Functional neuroimaging techniques such as single-positron emission computed tomography (SPECT) and positron emission tomography (PET) offer considerable scope for investigating disturbances of brain activity in psychiatric disorders. However, the heterogeneous nature of disorders such as schizophrenia limits the value of studies that group patient...

We describe a family-based sample of individuals with reading disability collected as part of a quantitative trait loci (QTL) mapping study. Eighty-nine nuclear families (135 independent sib-pairs) were identified through a single proband using a traditional discrepancy score of predicted/actual reading ability and a known family history. Eight cor...