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David A Collier

Publications and source records attributed to David A Collier.

At least 19 recordsLinked to original sources
PubMed2006

Reaction time of the Continuous Performance Test is an endophenotypic marker for schizophrenia: a study of first-episode neuroleptic-naive schizophrenia, their non-psychotic first-degree relatives and healthy population controls.

Sustained attention has been proposed as an endophenotype of schizophrenia, and consequently may be useful as a quantitative trait in genetic studies. In the present study, we used the continuous performance test (CPT) to measure sustained attention in 112 first-episode and neuroleptic-naive schizophrenic patients, 296 of their non-psychotic first-degree relatives, and 452 normal controls. Compared with controls, probands with schizophrenia showed worse performance on all measures of CPT. Parents, siblings and offspring of probands were also impaired on 'hit reaction time', an index of psychomotor processing speed of the correct response. Hit reaction time was also independent of the acute clinical features of the disease, indicating it is a trait rather than a state marker. Our findings supported the use of the hit reaction time measure of the CPT as an endophenotype marker for schizophrenia.

Adolescent↗
PubMed2006

Association study of CHRFAM7A copy number and 2 bp deletion polymorphisms with schizophrenia and bipolar affective disorder.

Schizophrenia and bipolar disorder are major psychiatric diseases that have a strong genetic element. Markers in the vicinity of the CHRNA7 gene at 15q13-q14 have been linked with an endophenotype of schizophrenia, P50 sensory gating disorder, with schizophrenia itself and with bipolar disorder. We have measured the copy number of the polymorphic partial duplication of CHRNA7 (CHRFAM7A) and genotyped a polymorphic 2 bp deletion within exon 6 of CHRFAM7A. In this study, 208 probands with a primary diagnosis of schizophrenia, 217 with a diagnosis of bipolar affective disorder and 28 with schizoaffective or other psychotic disorders were examined together with 197 controls recruited from the same region in Scotland. No significant association was seen for schizophrenia and bipolar disorder by genotype or allele overall for either polymorphism, but a mildly significant association by genotype (P = 0.04) was observed for absence of CHRFAM7A when the sample was analyzed as a single psychosis phenotype.

Base Sequence↗
PubMed2006

Difference in susceptibility to activity-based anorexia in two inbred strains of mice.

Food restricted rodents develop activity-based anorexia in the presence of a running wheel, characterised by increased physical activity, weight loss and decreased leptin levels. Here, we determined trait differences in the development of activity-based anorexia between C57BL/6J and DBA/2J inbred mouse lines previously reported as having low and high anxiety, respectively. C57BL/6J mice housed with running wheels and exposed to scheduled feeding reduced their wheel activity, in contrast to DBA/2J mice which exhibited increased behavioural activity under these conditions. Food restriction induced hypoleptinemia in both strains, but the decline in plasma leptin was stronger in DBA/2J mice and correlated with increased activity only in that strain. These data suggest that plasma leptin level dynamics rather than hypoleptinemia alone influences the development of activity-based anorexia and that recombinant inbred panels based on these progenitor lines offer opportunities for the identification of molecular determinants for anorexia nervosa related behavioural traits.

Animals↗
PubMed2006

Meta-analysis shows strong positive association of the neuregulin 1 (NRG1) gene with schizophrenia.

Chromosome 8p22-p11 has been identified as a locus for schizophrenia in several genome-wide scans and confirmed by meta-analysis of published linkage data. Systematic fine mapping using extended Icelandic pedigrees identified an associated haplotype in the gene neuregulin 1 (NRG1), also known as heuregulin, glial growth factor, NDF43 and ARIA. A 290 kb core at risk haplotype at the 5' end of the gene (HAP(ICE)), defined by five SNPs and two microsatellite polymorphisms was found to be associated with schizophrenia in the Icelandic and Scottish populations. A number of subsequent independent studies have attempted to replicate the association, and while some have been successful, the associated haplotype is not always HAP(ICE). Furthermore, no obviously functional or pathogenic variants have been identified, and the relationship between the gene and schizophrenia has remained inconclusive. To reconcile these conflicting findings and to give a comprehensive picture of the genetic architecture of this important gene, we performed a meta-analysis of 13 published population-based and family-based association studies up to November 2005. We analysed data from the SNP markers SNP8NRG241930, SNP8NRG243177, SNP8NRG221132 and SNP8NRG221533, and the microsatellite markers 478B14-848, 420M9-1395. Across these studies, strong positive association was found for all six polymorphisms. The haplotype analysis also showed significant association in the pooled international populations (OR=1.22, 95% CI 1.15-1.3, P=8 x 10(-10)). In Asian populations, the risk haplotype was focused around the two microsatellite markers, 478B14-848, 420M9-1395 (haplotype block B), and in Caucasian populations with the remaining four SNP markers (haplotype block A). This meta-analysis supports the involvement of NRG1 in the pathogenesis of schizophrenia, but with association between two different but adjacent haplotypes blocks in the Caucasian and Asian populations.

Asian People↗
PubMed2006

Behavioral, physiological, and molecular differences in response to dietary restriction in three inbred mouse strains.

Food restriction paradigms are widely used in animal studies to investigate systems involved in energy regulation. We have observed behavioral, physiological, and molecular differences in response to food restriction in three inbred mouse strains, C57BL/6J, A/J, and DBA/2J. These are the progenitors of chromosome substitution and recombinant inbred mouse strains used for mapping complex traits. DBA/2J and A/J mice increased their locomotor activity during food restriction, and both displayed a decrease in body temperature, but the decrease was significantly larger in DBA/2J compared with A/J mice. C57BL/6J mice did not increase their locomotor activity and displayed a large decrease in their body temperature. The large decline in body temperature during food restriction in DBA/2J and C57BL/6J strains was associated with a robust reduction in plasma leptin levels. DBA/2J mice showed a marked decrease in white and brown adipose tissue masses and an upregulation of the antithermogenic hypothalamic neuropeptide Y Y(1) receptor. In contrast, A/J mice showed a reduction in body temperature to a lesser extent that may be explained by downregulation of the thermogenic melanocortin 3 receptor and by behavioral thermoregulation as a consequence of their increased locomotor activity. These data indicate that genetic background is an important parameter in controlling an animal's adaptation strategy in response to food restriction. Therefore, mouse genetic mapping populations based on these progenitor lines are highly valuable for investigating mechanisms underlying strain-dependent differences in behavioral physiology that are seen during reduced food availability.

Adipose Tissue↗
PubMed2006

Evaluation of a susceptibility gene for schizophrenia: genotype based meta-analysis of RGS4 polymorphisms from thirteen independent samples.

BACKGROUND: Associations between schizophrenia (SCZ) and polymorphisms at the regulator of G-protein signaling 4 (RGS4) gene have been reported (single nucleotide polymorphisms [SNPs] 1, 4, 7, and 18). Yet, similar to other SCZ candidate genes, studies have been inconsistent with respect to the associated alleles. METHODS: In an effort to resolve the role for RGS4 in SCZ susceptibility, we undertook a genotype-based meta-analysis using both published and unpublished family-based and case-control samples (total n = 13,807). RESULTS: The family-based dataset consisted of 10 samples (2160 families). Significant associations with individual SNPs/haplotypes were not observed. In contrast, global analysis revealed significant transmission distortion (p = .0009). Specifically, analyses suggested overtransmission of two common haplotypes that account for the vast majority of all haplotypes. Separate analyses of 3486 cases and 3755 control samples (eight samples) detected a significant association with SNP 4 (p = .01). Individual haplotype analyses were not significant, but evaluation of test statistics from individual samples suggested significant associations. CONCLUSIONS: Our collaborative meta-analysis represents one of the largest SCZ association studies to date. No individual risk factor arose from our analyses, but interpretation of these results is not straightforward. Our analyses suggest risk due to at least two common haplotypes in the presence of heterogeneity. Similar analysis for other putative susceptibility genes is warranted.

Case-Control Studies↗
PubMed2006

The quantification of COMT mRNA in post mortem cerebellum tissue: diagnosis, genotype, methylation and expression.

BACKGROUND: The COMT gene is located on chromosome 22q11, a region strongly implicated in the aetiology of several psychiatric disorders, in particular schizophrenia. Previous research has suggested that activity and expression of COMT is altered in schizophrenia, and is mediated by one or more polymorphisms within the gene, including the functional Val158Met polymorphism. METHOD: In this study we examined the expression levels of COMT mRNA using quantitative RT-PCR in 60 post mortem cerebellum samples derived from individuals with schizophrenia, bipolar disorder, depression, and no history of psychopathology. Furthermore, we have examined the methylation status of two CpG sites in the promoter region of the gene. RESULTS: We found no evidence of altered COMT expression or methylation in any of the psychiatric diagnoses examined. We did, however, find evidence to suggest that genotype is related to COMT gene expression, replicating the findings of two previous studies. Specifically, val158met (rs165688; Val allele) rs737865 (G allele) and rs165599 (G allele) all showed reduced expression (P < 0.05). Finally, we observe a strong sexual dimorphism in COMT expression, with females exhibiting significantly greater levels of COMT mRNA. CONCLUSION: The expression of COMT does not appear to be altered in the cerebellum of individuals suffering from schizophrenia, bipolar disorder or depression, but does appear to be influenced by single nucleotide polymorphisms within the gene.

Bipolar Disorder↗
PubMed2006

Bipolar 1 disorder is not associated with the RGS4, PRODH, COMT and GRK3 genes.

Although current psychiatric nosology separates bipolar disorder and schizophrenia into non-overlapping categories, there is growing evidence of a partial aetiological overlap between them from linkage, genetic epidemiology and molecular genetics studies. Thus, it is important to determine whether genes implicated in the aetiology of schizophrenia play a role in bipolar disorder, and vice versa. In this study we investigated a total of 15 single nucleotide polymorphisms (SNPs), and all possible haplotypes, of genes that have been previously implicated in schizophrenia or bipolar disorder - RGS4, PRODH, COMT and GRK3 - in a sample of 213 cases with bipolar affective disorder type 1 and 197 controls from Scotland. We analysed the polymorphisms allele-wise, genotype-wise and, for each gene, haplotype-wise but obtained no result that reached nominal significance (p<0.05) for an association with the disease status. In conclusion, we could not find evidence of association between RGS4, PRODH, COMT and GRK3 genes and bipolar affective disorder 1 in the Scottish population.

Bipolar Disorder↗
PubMed2006

Episodic memory performance predicted by the 2bp deletion in exon 6 of the "alpha 7-like" nicotinic receptor subunit gene.

OBJECTIVE: There is evidence of linkage between chromosome 15q14 and the P50 auditory evoked response, a heritable neuropsychological marker associated with increased risk of schizophrenia. Chromosome 15q14 harbors the alpha-7 nicotinic receptor subunit gene (CHRNA7) and a hybrid gene of unknown function (CHRFAM7A). CHRNA7 is involved in memory formation, a core dysfunction in schizophrenia. The authors set out to determine if this locus is associated with memory dysfunction in schizophrenia. METHOD: A 2bp deletion in exon 6 of CHRFAM7A, which disrupts the hybrid gene and has previously been associated with P50 deficit, was genotyped in 251 individuals from the Maudsley Family Study of schizophrenia. Episodic memory function was assessed using the Wechsler Memory Scale. RESULTS: Significant associations were identified with delayed recall and percentage retained, with the presence of the deletion predicting worse performance. CONCLUSIONS: These observations indicate that episodic memory function is a schizophrenia endophenotype and implicate the CHRFAM7A/CHRNA7 locus in modulating its function.

Chromosome Mapping↗
PubMed2005

Influence of X chromosome and hormones on human brain development: a magnetic resonance imaging and proton magnetic resonance spectroscopy study of Turner syndrome.

BACKGROUND: Women with Turner syndrome (TS; 45,X) lack a normal second X chromosome, and many are prescribed exogenous sex and growth hormones (GH). Hence, they allow us an opportunity to investigate genetic and endocrine influences on brain development. METHODS: We examined brain anatomy and metabolism in 27 adult monosomic TS women and 21 control subjects with volumetric magnetic resonance imaging and magnetic resonance spectroscopy. RESULTS: In TS women, regional gray matter volume was significantly smaller in parieto-occipital cortex and caudate nucleus and larger in cerebellar hemispheres. White matter was reduced in the cerebellar hemispheres, parieto-occipital regions, and splenium of the corpus callosum but was increased in the temporal and orbitofrontal lobes and genui of corpus callosum. Women with TS had a significantly lower parietal lobe concentration of N-acetyl aspartate, and higher hippocampal choline. Also, among women with TS, there were significant differences in regional gray matter volumes and/or neuronal integrity, depending upon parental origin of X chromosome and oxandrolone and GH use. CONCLUSIONS: X chromosome monosomy, imprinting and neuroendocrine milieu modulate human brain development-perhaps in a regionally specific manner.

Adult↗
PubMed2005

Association between BDNF val66 met genotype and episodic memory.

The val66 met polymorphism of brain derived neurotrophic factor (BDNF) has been associated with variability in episodic memory [Egan et al., 2003]. In an attempt to replicate this finding, we genotyped 206 individuals (92 affected with schizophrenia or a related disorder and 114 unaffected relatives) from the Maudsley Family Study for the BDNF val66 met polymorphism. We analyzed the effect of this polymorphism on episodic memory using the Wechsler Memory Scale, revised version (WMS-R) by regression analysis between the WMS delayed score of logical memory and genotype (corrected for age, sex, and IQ). We found the met66 allele conferred a lower score on the WMS delayed measure (R2 = 0.014 P = 0.09), which was not significant. When cases and unaffected relatives were analyzed separately, met66 was associated with a lower score on the WMS delayed measure in the relatives only (R2 = 0.077 P = 0.01), which is consistent with previous findings.

Algorithms↗
PubMed2005

Association of BDNF with restricting anorexia nervosa and minimum body mass index: a family-based association study of eight European populations.

Eating disorders (ED), such as anorexia nervosa (AN) and bulimia nervosa (BN), are complex psychiatric disorders where different genetic and environmental factors are involved. Several lines of evidence support that brain-derived neurotrophic factor (BDNF) plays an essential role in eating behaviour and that alterations on this neurotrophic system participates in the susceptibility to both AN and BN. Accordingly, intraventricular administration of BDNF in rats determines food starvation and body weight loss, while BDNF or its specific receptor NTRK2 knockout mice develop obesity and hyperphagia. Case-control studies also suggest a BDNF contribution in the aetiology of ED: we have previously reported a strong association between the Met66 variant within the BDNF gene, restricting AN (ANR) and minimum body mass index (minBMI) in a Spanish sample, and a positive association between the Val66Met and -270C/T BDNF SNPs and ED in six different European populations. To replicate these results, avoiding population stratification effects, we recruited 453 ED trios from eight European centres and performed a family-based association study. Both haplotype relative risk (HRR) and haplotype-based haplotype relative risk (HHRR) methods showed a positive association between the Met66 allele and ANR. Consistently, we also observed an effect of the Met66 variant on low minBMI and a preferential transmission of the -270C/Met66 haplotype to the affected ANR offspring. These results support the involvement of BDNF in eating behaviour and further suggest its participation in the genetic susceptibility to ED, mainly ANR and low minBMI.

Adult↗
PubMed2004

Association analysis of the DRD4 and COMT genes in methamphetamine abuse.

We analyzed two polymorphisms in genes encoding proteins of the dopamine system, the Val158Met polymorphism in the catechol-O-methyltransferase gene and the 120-bp VNTR polymorphism in the promoter of the dopamine D4 receptor gene for association with methamphetamine abuse. We used a case/control design with 416 methamphetamine abusing subjects and 435 normal controls. All subjects were Han Chinese from Taiwan. We found an excess of the high activity Val158 allele in the methamphetamine abuser group, consistent with several previous reports of association of this allele with drug abuse. The 120-bp VNTR polymorphism in the promoter of the dopamine D4 receptor gene itself did not show significant association with methamphetamine abuse. However, analysis of the 120-bp VNTR polymorphism and the exon 3 VNTR in the dopamine D4 receptor as a haplotype showed significant association with methamphetamine abuse, which gave an empirical P value 0.0034 for a heterogeneity model. Moreover, there were significant interactive effects between polymorphisms in the catechol-O-methyltransferase and dopamine D4 genes. The evidence of interaction between COMT 158 Val/Met and DRD4 48-bp VNTR polymorphisms (P = 0.0003, OR = 1.45, 95% CI: 1.148-1.77), and between COMT 158 Val/Met and DRD4 120 bp promoter polymorphisms (P = 0.01, OR = 1.10, 95% CI: 1.10-1.18) were significant but the latter was weak. We conclude that genetic variation in the dopamine system may encode an additive effect on risk of becoming a methamphetamine abuser.

Adolescent↗
PubMed2004

Evidence for association between novel polymorphisms in the PRODH gene and schizophrenia in a Chinese population.

Haploinsufficiency for or mutation in at least one gene from the velocardiofacial syndrome (VCFS) region at chromosome 22q11 is implicated in psychosis. Linkage disequilibrium mapping of the region in patients identified a segment containing two genes, proline dehydrogenase (PRODH) and DGCR6, as candidates [Liu et al., 2002a] and by analysis of additional polymorphisms the PRODH gene was associated with schizophrenia in adult and early onset patients. In the present study we provide additional evidence in support of genetic association between PRODH and schizophrenia in a Chinese population. We analyzed the PRODH gene in a samples of schizophrenic patients and their families from Sichuan, SW China consisting of 528 family trios and sibling pairs. We genotyped six SNPs, PRODH*1195C-->T, PRODH*1482C-->T, PRODH*1483A-->G, PRODH*1766A-->G, PRODH*1852G-->A PRODH*1945T-->C, two of which (PRODH*1483A-->G and PRODH*1852G-->A) have not been previously reported. We found association with schizophrenia for two haplotypes consisting of PRODH*1945T-->C and PRODH*1852G-->A (Global P = 0.006), and PRODH*1852G-->A and PRODH*1766A-->G (Global P = 0.01) which include one of the newly identified markers. After six-fold Bonferroni correction for multiple testing the PRODH*1945T-C/PRODH*1852G-A haplotypes remained significant. This is a sub-haplotype of the PRODH haplotype previously associated with schizophrenia and it also maps to the 3' region of the gene, indicating that this is the region most likely to contain the underlying risk alleles. Overall this finding supports a role for the PRODH locus in schizophrenia.

Alleles↗
PubMed2004

Association of BDNF with anorexia, bulimia and age of onset of weight loss in six European populations.

Several genes with an essential role in the regulation of eating behavior and body weight are considered candidates involved in the etiology of eating disorders (ED), but no relevant susceptibility genes with a major effect on anorexia nervosa (AN) or bulimia nervosa (BN) have been identified. Brain-derived neurotrophic factor (BDNF) has been implicated in the regulation of food intake and body weight in rodents. We previously reported a strong association of the Met66 allele of the Val66Met BDNF variant with restricting AN (ANR) and low minimum body mass index in Spanish patients. Another single nucleotide polymorphism located in the promoter region of the BDNF gene (-270C>T) showed lack of association with any ED phenotype. In order to replicate these findings in a larger sample, we performed a case-control study in 1142 Caucasian patients with ED consecutively recruited in six different centers from five European countries (France, Germany, Italy, Spain and UK) participating in the 'Factors in Healthy Eating' project. We have found that the Met66 variant is strongly associated to all ED subtypes (AN, ANR, binge-eating/purging AN and BN), and that the -270C BDNF variant has an effect on BN and late age at onset of weight loss. These are the first two variants associated with the pathophysiology of ED in different populations and support a role for BDNF in the susceptibility to aberrant eating behaviors.

Age of Onset↗
PubMed2004

Cognitive flexibility in anorexia nervosa and bulimia nervosa.

The aim of this study was to determine if there are differences in cognitive flexibility in anorexia nervosa and bulimia nervosa. Fifty-three patients with an eating disorder (34 with anorexia nervosa and 19 with bulimia nervosa) and 35 healthy controls participated in the study. A battery of neuropsychological tests for cognitive flexibility was used, including Trail Making B, the Brixton Test, Verbal Fluency, the Haptic Illusion Test, a cognitive shifting task (CatBat) and a picture set test. Using exploratory factor analysis, four factors were obtained: 1: Simple Alternation; 2: Mental Flexibility; 3: Perseveration; and 4: Perceptual Shift. Patients with anorexia nervosa had abnormal scores on Factors 1 and 4. Patients with bulimia nervosa showed a different pattern, with significant impairments in Factors 2 and 4. These findings suggest that differential neuropsychological disturbance in the domain of mental flexibility/rigidity may underlie the spectrum of eating disorders.

Adult↗