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A J Richardson

Publications and source records attributed to A J Richardson.

At least 19 recordsLinked to original sources
PubMed2006

Further evidence that the KIAA0319 gene confers susceptibility to developmental dyslexia.

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 two large, independent UK samples, we obtained only weak, inconsistent evidence for their involvement in DD. Having previously found evidence that variation in the KIAA0319 gene confers susceptibility to DD, we sought to refine this genetic association by genotyping 36 additional SNPs in the gene. Nine SNPs, predominantly clustered around the first exon, showed the most significant association with DD in one or both UK samples, including rs3212236 in the 5' flanking region (P = 0.00003) and rs761100 in intron 1 (P = 0.0004). We have thus refined the region of association with developmental dyslexia to putative regulatory sequences around the first exon of the KIAA0319 gene, supporting the presence of functional mutations that could affect gene expression. Our data also suggests a possible interaction between KIAA0319 and DCDC2, which requires further testing.

5' Untranslated Regions↗
PubMed2006

Distribution of inland wetlands with sulfidic sediments in the Murray-Darling Basin, Australia.

This project examined the extent of sulfidic sediments in freshwater wetlands of the Murray-Darling Basin, Australia. We sampled 81 wetlands throughout the basin with methods previously developed for the analysis of coastal acid sulfate soils. Sulfidic sediments are generally regarded as a coastal phenomenon. We tested the hypothesis that elevated concentrations of mineral sulfides may also accumulate in sediments of inland wetlands. Of the 81 wetlands sampled, 17 (21%) contained reduced sulfur in sediments at concentrations above suggested trigger values. Most of the affected wetlands were adjacent to the Murray River, with only several associated with other major river catchments. Reduced sulfur in the sediments was positively correlated with sulfate concentrations in the overlying water column. This represents a concern for wetland managers because of the increasing desire to return wetlands to a more natural wetting and drying cycle to improve wetland health. However, during drying, sulfidic sediments oxidise and produce acid, which may exceed the buffering capacity of the system and ultimately harm aquatic life. Therefore, if sulfidic sediments are present, a drying phase should only be reinstated after careful consideration of the potential acidification risks. This study verified that sulfidic sediments can occur in freshwater wetlands in concentrations that could pose an ecological risk if mismanaged.

Australia↗
PubMed2006

Ruptured splenic artery aneurysm in pregnancy presenting in a manner similar to pulmonary embolus.

We report a patient, 33 weeks pregnant with twins, who sustained a ruptured splenic artery aneurysm. This presented with left sided chest pain, breathlessness, low oxygen saturations and electrocardiogram (ECG) changes supportive of a diagnosis of massive pulmonary embolus. The diagnosis of splenic artery rupture was made at emergency Caesarean section performed for fetal distress.

Adolescent↗
PubMed2005

Schizophrenia syndromes associated with changes in ventricle-to-brain ratios: a serial high-resolution three-dimensional magnetic resonance imaging study in first-episode schizophrenia patients using subvoxel registration and semiautomated quantification.

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 intervals. The application of subvoxel registration and semiautomated quantification techniques demonstrated a significantly different outcome in ventricular changes between the two groups of patients. Compared with the controls, the withdrawn patients showed progressive ventricular enlargement, with an increase in ventricle-to-brain volume ratio, whereas the active group showed a reduction in ventricle-to-brain volume ratio, with a change opposite in sign and smaller in magnitude. These findings lend further support for the aetiological validity of this syndromal model of schizophrenia and are likely to be of importance in furthering our understanding of its pathogenesis and in the development of suitable therapeutic strategies.

Adult↗
PubMed2004

Cerebral metabolism in male patients with schizophrenia who have seriously and dangerously violently offended: a 31P magnetic resonance spectroscopy study.

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 resonance spectroscopy was carried out in 15 male patients with schizophrenia who had violently offended (homicide, attempted murder, or wounding with intent to cause grievous bodily harm) while psychotic and in a control group of 13 age-matched healthy male control subjects. Spectra were obtained from 70x70x70mm(3) voxels in the brain using an image-selected in vivo spectroscopy pulse sequence. betaNTP was lower (P < 0.04) and gammaNTP was higher (P < 0.04) in the patient group compared with the normal control group. Our results are suggestive of increased cerebral energy metabolism taking place in the forensic patients.

Adult↗
PubMed2004

Clinical trials of fatty acid treatment in ADHD, dyslexia, dyspraxia and the autistic spectrum.

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 from intervention studies in the form of randomised, double-blind, placebo-controlled trials. Published studies of this kind are still fairly few in number, and mainly involve the diagnostic categories of ADHD and dyslexia, although other trials involving individuals with dyspraxia or ASD are in progress. The main findings to date from such studies are reviewed and evaluated here with the primary aim of guiding future research, although given that fatty acid supplementation for these conditions is already being adopted in many quarters, it is hoped that some of the information provided may also help to inform clinical practice.

Apraxias↗
PubMed2003

Omega-3 and omega-6 fatty acid concentrations in red blood cell membranes relate to schizotypal traits in healthy adults.

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 and fatty acid composition of their venous blood samples was analysed via gas-liquid chromatography. Correlations between schizotypy measures and RBC fatty acids were examined and comparisons made between groups high and low on fatty acid measures and schizotypy scores. The omega-6 fatty acids arachidonic, adrenic and docosapentaenoic acid were directly related to positive schizotypal trait measures, as were most omega-3 fatty acids, but none were related to a negative, withdrawn form of schizotypy. Our findings of high RBC concentrations of omega-3 and omega-6 fatty acids in healthy adults with positive schizotypal traits clearly contrast with the low levels often found in schizophrenia, but are quite consistent with evidence that omega-3 fatty acids (notably EPA) can be useful in the treatment of schizophrenic illness.

Adolescent↗
PubMed2002

Auditory frequency discrimination in adult developmental dyslexics.

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) and a variant with six A-stimuli per trial (2I_6A_X) were used here. Frequency varied around 500 Hz; interstimulus interval (ISI) ranged between 0 and 1,000 msec. Under 2I_1A_X, dyslexics always had larger just noticeable differences (JNDs) than did controls. Dyslexic and control JNDs were equal at shorter ISIs under 2I_6A_X, but dyslexics became worse than controls at longer ISIs. Signal detection analysis suggests that both sensory variance and trace variance are larger in dyslexics than in controls.

Adult↗
PubMed2001

SPECT neuroimaging in schizophrenia with religious delusions.

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 patients under this global label. Some have addressed this problem by considering schizophrenia at a syndromal level, but so far, few have focussed at the level of individual symptoms. We describe the first neuroimaging study of the specific symptom of religious delusions in schizophrenia. 99mTc HMPAO high-resolution SPECT neuroimaging showed an association of religious delusions with left temporal overactivation and reduced occipital uptake, particularly on the left.

Adult↗
PubMed2001

Associations between central and peripheral measures of phospholipid breakdown revealed by cerebral 31-phosphorus magnetic resonance spectroscopy and fatty acid composition of erythrocyte membranes.

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 phosphorus magnetic resonance spectroscopy (31P MRS) studies; and erythrocyte membrane fatty acid concentrations. Thus far, there have been no studies comparing these two indices to ascertain the extent to which they agree. 2. The authors measured these indices in nine normal adults. Spectral localization was achieved using four-dimensional chemical shift imaging methods and erythrocyte membrane fatty acid concentrations (from blood samples taken at the time of scanning) were measured using gas liquid chromatography. 3. Levels of PDE (an index of phospholipid catabolism), measured using cerebral 31P MRS, were significantly correlated with reduced concentrations of the highly unsaturated fatty acids docosahexaenoic acid (DHA) (r = -0.68, p < 0.05) and eicosapentaenoic acid (EPA) (r -0.78, p < 0.02). No significant correlations were found between peripheral concentrations of any highly unsaturated fatty acids and PME levels, nor between their essential fatty acid precursors and either PDE or PME levels. Other 31-phosphorus metabolites also showed no significant correlations with the blood fatty acid measures. 4. The correlations between central measures of PDE and peripheral measures of DHA and EPA provide validation of cerebral 31P MRS as a non-invasive technique for the study of membrane phospholipid metabolism in vivo.

Adult↗
PubMed2001

Investigation of quantitative measures related to reading disability in a large sample of sib-pairs from the UK.

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 correlated psychometric measures were administered to each sibling, including single word reading, spelling, similarities, matrices, spoonerisms, nonword and irregular word reading, and a pseudohomophone test. Summary statistics for each measure showed a reduced mean for the probands compared to the co-sibs, which in turn was lower than that of the population. This partial co-sib regression back to the mean indicates that the measures are influenced by familial factors and therefore, may be suitable for a mapping study. The variance of each of the measures remained largely unaffected, which is reassuring for the application of a QTL approach. Multivariate genetic analysis carried out to explore the relationship between the measures identified a common factor between the reading measures that accounted for 54% of the variance. Finally the familiality estimates (range 0.32-0.73) obtained for the reading measures including the common factor (0.68) supported their heritability. These findings demonstrate the viability of this sample for QTL mapping, and will assist in the interpretation of any subsequent linkage findings in an ongoing genome scan.

Child↗
PubMed2001

Could platelet activating factor play a role in developmental dyslexia?

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. Platelet-activating factor (PAF) is a pro-inflammatory lipid implicated in neurological disorders. We propose that PAF may also be involved in dyslexia.

Brain↗
PubMed2001

Perinatal inferior vena cava thrombosis and absence of the infrarenal inferior vena cava.

We report a case of infrarenal absence of the inferior vena cava (IVC) presenting as a major iliofemoral deep venous thrombosis in an adolescent. This is the first report of infrarenal IVC absence in which IVC thrombosis has been demonstrated in the perinatal period. We propose an association between perinatal IVC thrombosis and subsequent infrarenal IVC absence. In addition, the case demonstrates the importance of assessment for anatomical anomalies in patients presenting with apparently idiopathic deep venous thrombosis.

Child↗
PubMed2001

Eicosapentaenoic acid in treatment-resistant depression associated with symptom remission, structural brain changes and reduced neuronal phospholipid turnover.

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 months later. The addition of ethyl-EPA led to a dramatic and sustained clinical improvement in all the symptoms of depression, including a cessation of previously unremitting severe suicidal ideation, within one month. Symptoms of social phobia also improved dramatically. During the nine-month period the volumetric niacin response increased by 30%, the relative concentration of cerebral phosphomonesters increased by 53%, and the ratio of cerebral phosphomonesters to phosphodiesters increased by 79%, indicating reduced neuronal phospholipid turnover. Registered difference images showed that the EPA treatment was accompanied by structural brain changes including, in particular, a reduction in the lateral ventricular volume.

Adult↗
PubMed2000

Chromosomal integration of the green fluorescent protein gene in lactic acid bacteria and the survival of marked strains in human gut simulations.

An integration vector was constructed to allow introduction of the gfp gene into the chromosomes of Gram-positive bacteria. Integration depends on homologous recombination between a short 458-nt sequence of the tet(M) gene in the vector and a copy of Tn916 in the host chromosome. Strains of Lactococcus lactis IL1403, Enterococcus faecalis JH2-SS, and Streptococcus gordonii DL1 stably marked with single chromosomal copies of the gfp were readily visualised by epifluorescence microscopy. The marked L. lactis strain survived poorly in a continuous culture system inoculated with human faecal flora, while the laboratory E. faecalis strain was lost at approximately the dilution rate of the fermenter.

Bacteria↗
PubMed2000

Red cell and plasma fatty acid changes accompanying symptom remission in a patient with schizophrenia treated with eicosapentaenoic acid.

The administration of the omega-3 fatty acid eicosapentaenoic acid (EPA) to a drug-naïve patient with schizophrenia, untreated with conventional antipsychotic medication, led to a dramatic and sustained clinical improvement in both positive and negative symptoms. This was accompanied by a correction in erythrocyte membranes of abnormalities in both n-3 and n-6 highly unsaturated fatty acids (HUFAs). Therefore EPA is able to reverse the phospholipid abnormalities previously described in schizophrenia. This reversal is associated with, and is likely to be the cause of, the clinical improvement. In particular, EPA appears to have reversed the depletion of not only n-3 HUFAs, but also of membrane arachidonic acid, possibly via inhibition of HUFA-specific phospholipase A(2), an enzyme which removes HUFAs from the S(N)2 position of membrane phospholipids, or by activation of a fatty acid coenzyme A ligase. Correction by EPA of abnormalities in both enzyme systems is not ruled out.

Adult↗
PubMed2000

Monocular occlusion can improve binocular control and reading in dyslexics.

Developmental dyslexia is a neurodevelopmental condition which causes 5-10% of children to have unexpected difficulty learning to read. Many dyslexics have impaired development of the magnocellular component of the visual system, which is important for timing visual events and controlling eye movements. Poor control of eye movement may lead to unstable binocular fixation, and hence unsteady vision; this could explain why many dyslexics report that letters appear to move around, causing visual confusion. Previous research has suggested that such binocular confusion can be permanently alleviated by temporarily occluding one eye. The aim of the present study was therefore to assess the binocular control and reading progress of dyslexic children with initially unstable binocular control after the left eye was patched. One hundred and forty-three dyslexics were studied. They were selected from children aged 7-11 years referred to a learning disabilities clinic if they were dyslexic and had unstable binocular control. They were randomly assigned to wear yellow spectacles with or without the left lens occluded, and were followed for 9 months. Significantly more of the children who were given occlusion gained stable binocular fixation in the first 3 months (59%) compared with children given the unoccluded glasses (36%). This advantage was independent of IQ or initial reading ability. Furthermore, at all the 3-month follow-ups, children were more likely to have gained stable binocular control if they had been wearing the occluded glasses. Gaining stable binocular control significantly improved reading. The children who did so with the help of occlusion improved their reading by 9.4 months in the first 3 months, compared with 3.9 months in those who were not patched and did not gain stable fixation. Over the whole 9 months, children who received occlusion and gained stable fixation nearly doubled their rate of progress in reading compared with those who remained unstable. At all the follow-ups the reading of those given occlusion was significantly better than that of those not occluded. Thus monocular occlusion helped children with unstable binocular control to gain good binocular fixation. If they gained stability, they made significantly faster reading progress. The progress made by the children who gained stable fixation was much greater than that achieved with other remedial techniques.

Child↗