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David A Collier

Publications and source records attributed to David A Collier.

31 records · Page 2Linked to original sources
PubMed2003

The genetics of schizophrenia: glutamate not dopamine?

The major targets of current drugs used in mental health, such as neurotransmitter receptors and transporters, are based on serendipitous findings from several decades ago, and there is currently a severe drought of new drug targets. There is a pressing need for novel drugs, and much hope has been placed on the use of molecular genetics to help define them. However, despite evidence for a genetic basis to schizophrenia stretching back for over a century, and a heritability of about 80%, the identification of susceptibility genes has been an uphill struggle. Candidate gene studies, which have generally focussed on obvious candidates from the dopamine and serotonin systems, as well as genes involved in brain development, have not generally been successful, although meta-analysis indicates that the dopamine D3 receptor gene (DRD3) and the serotonin receptor gene type 2A (HTR2A) may have a very small influence on risk. Linkage analysis has provided robust evidence of genetic loci, for example, on chromosomes 8p, 13q and 22q, and also implies shared genetic aetiology with bipolar disorder. The identification of these loci together with advances in genetic technology, especially the characterisation of polymorphisms, the understanding of haplotypes and the development of statistical methods, has lead to the identification of several plausible susceptibility genes, including neuregulin 1, proline dehydrogenase and dysbindin. Interestingly, these genes point more towards a role for the glutamate pathway rather than the dopamine pathway in schizophrenia. We have attempted to replicate some of these findings in schizophrenic patients from SW China, and we find significant association with a novel neuregulin 1 haplotype, with proline dehydrogenase polymorphisms, but not with catechol-O-methyltransferase (COMT). The replication of neuregulin 1 association on chromosome 8p by several investigators is the most convincing to date, and the presence of a syndrome similar to dementia praecox of 8p linked families, and the lack of linkage of bipolar disorder to this region is a testament to the ideas of Kraepelin more than 100 years ago.

Animals↗
PubMed2003

Association of the 5-HT2c gene with susceptibility and minimum body mass index in anorexia nervosa.

The association between a non-conservative Cys23Ser in the 5-HT2c gene and anorexia nervosa in females was examined. We used case-controls and family based association analysis in a sample of 118 patients with DSMIV anorexia nervosa, 244 controls and 47 family trios. There was a significant increase in the frequency of the Ser23 allele in the patients by allele (18.8% vs 12.8%; p = 0.026; OR 1.58, 95% CI 1.0-2.4) and genotype (32.2% vs 19.9%; genotype-wise p = 0.027). There was significant correlation between genotype and minimum BMI (r2 = 0.056; p = 0.01), indicating that the Ser23 allele has an effect on severity of illness. We performed TDT analysis using a sub-sample of the cases (58) for whom both parents were available and we found an excess transmission of the Ser23 allele (p = 0.05). Our findings are consistent a role for the Ser23 allele of 5-HT2c in mediating susceptibility to and increasing severity of anorexia nervosa.

Alleles↗
PubMed2003

Paraoxonase in Persian Gulf War veterans.

Serum paraoxonase (PON1) is responsible for the metabolism of organophosphates in serum, and PON1 activity is a major determinant of their toxicity in humans. There have been reports linking lowered PON1 activity to physical symptoms after deployment to the Persian Gulf War (PGW) of 1990 to 1991. Therefore, the object of this study was to determine (1) whether PON1 activity was decreased among symptomatic PGW veterans compared with asymptomatic PGW veterans and (2) to determine whether PGW veterans as a whole had lower PON1 activity compared with other military control groups. This was a case control study nested in occupational cohort study of military personnel. Four groups of military personnel were identified from a large epidemiological study of health effects of deployment to the PGW and Bosnia: (1) symptomatic PGW veterans, n = 115; (2) healthy PGW veterans, n = 95; (3) symptomatic Bosnia peacekeeping veterans, n = 52; and (4) symptomatic nondeployed military controls, n = 85. The main outcome measures were PON1 activity and genotype for PON1-55 and -192. We found significant differences in PON1 activity among these four groups, and although the two Gulf groups did not differ in PON1 activity, those deployed to the Gulf had significantly lower PON1 activity compared with the non-PGW groups (median difference = 70.9; 95% CI: 20.2, 121.5, P = 0.012). These differences were not explained by a range of potential confounders, or differences in PON1 coding region polymorphisms. PON1 activity is reduced in PGW veterans compared with military control groups. The effect is independent of ill health in PGW veterans.

Adult↗
PubMed2003

Mutation screening and association analysis of the parkin gene in Parkinson's disease patients from South-West China.

Various deletions and point mutations in the Parkin gene have been strongly associated with Parkinson's disease (PD) and parkinsonism, especially when the onset occurs at a young age. In this study, we screened 25 "early-onset" (<49 years at onset) and 91 later-onset PD patients from a Han Chinese population from South-West China for deletions and mutations in the Parkin gene. We found no deletions or point mutations in exons 1-12 of the Parkin gene using direct sequence analysis and only detected the common Ser167Asn polymorphism. We analysed Ser167Asn in 116 patients with sporadic PD and 124 controls, matched for age and gender. There were significant differences in allele and genotype frequency between PD patients, with the 167Asn allele more common in cases than controls (46.6 vs. 35.1%; chi(2) = 6.54, p = 0.011, odds ratio = 1.61, 95% confidence interval, CI, 1.10-2.37), as was the 167Asn genotype (17.3 vs. 11.3%; p = 0.04). The frequency of the 167Ser genotype was significantly lower in PD patients than in controls when compared with that of the other two genotypes combined (chi(2) = 7.84, p = 0.005, odds ratio = 0.46, 95% CI 0.25 - 0.82). No significant differences in the frequencies of the allele and genotypes were found between patients classified into two groups according to symptoms at onset (chi(2) = 0.191, p = 0.66, odds ratio = 1.12, 95% CI 0.65-1.95; chi(2) = 0.24, p = 0.887) or age of onset (p = 0.787). In summary, homozygous deletion mutations and point mutations in exons 1-12 of the Parkin gene were not detected in this Han Chinese population, although we cannot exclude compound heterozygous deletions. In addition, our study suggests that the variant 167Asn increases the risk of developing PD.

Adult↗
PubMed2003

Pharmacogenetics in psychosis.

Pharmacogenetics uses genetic information to tailor drug treatment to the individual, maximizing clinical response and minimizing side effects. Failure to respond to medication and adverse side effects are common problems in psychiatry. Intolerable side effects can lead to discontinuation of medication. Individual genetic differences can determine both clinical responses to medications and the adverse side effects experienced. To fully predict clinical response to psychotropic drug treatment we must consider social, demographic and clinical factors such as compliance, social support and history of birth trauma, in addition to genetic influence on susceptibility and etiology.

Antipsychotic Agents↗
PubMed2003

Personality disorders and personality dimensions in anorexia nervosa.

Information on the relationship between anorexia nervosa (AN) and personality disorders (PDs) and dimensions of temperament and character (measured by the Temperament and Character Inventory [TCI; Cloninger, Przybeck Svrakic, & Wetzel, 1994]) is limited. This study examines the predictive validity of the TCI for PD diagnoses assessed by the International Personality Disorder Examination-ICD-10 (IPDE-ICD-10; Loranger, Janca, & Sartorius, 1997) interviews of 46 women with DSM-IV-defined AN. Patients with a PD reported higher levels of harm-avoidance and lower levels of self-directedness than those without a PD. Scores on the TCI were predictive of the number of PD features present, particularly for those PDs in the anankastic, anxious, and dependent groups accounting for 40% to 51% of the variance. Cluster analysis based on scores on the TCI identified a subgroup of patients characterized by low levels of novelty seeking, self-directedness, and cooperativeness and high levels of harm avoidance. This cluster included the majority of those with avoidant, anxious, or dependent PDs. Assessment of particular personality dimensions was able to predict PDs in an anorexic sample. Since normal personality dimensions have greater validity than the categorical PDs, a consideration of normal temperament and character may assist in clinical decisionmaking and considerations concerning treatment.

Adult↗
PubMed2002

Allelic association analysis of the dopamine D2, D3, 5-HT2A, and GABA(A)gamma2 receptors and serotonin transporter genes with heroin abuse in Chinese subjects.

Five candidate genes, the receptors DRD2, DRD3, HTR2A and GABA(A)gamma2, and the serotonin transporter (5-HTT) were analyzed for association with heroin abuse. We examined three polymorphisms (promoter - 141DeltaC, Ser311Cys, and TaqI) in the DRD2 gene, one polymorphism (Ser9Gly) in the DRD3 gene, two polymorphisms (promoter - 1438G/A and T102C) in the HTR2A gene, two polymorphisms (VNTR and Del/Ins) in 5-HTT gene, and one polymorphism (G3145A) in GABA(A)gamma2 gene in 121 Chinese heroin addicts and 194 controls. None of the polymorphisms differed significantly for allele, genotype, or haplotype frequencies, except for the DRD2 promoter polymorphism - 141DeltaC (genotype-wise and allele-wise, P = 0.05, uncorrected). An additional 344 subjects with heroin abuse and 104 controls were investigated for the - 141DeltaC polymorphism. In the second sample, there were no significant difference of genotype or allele frequencies between subjects with heroin abuse and normal controls. When we divided the sample by route of administration into nasal inhalers and IM or IV injectors, however, it produced a significant difference between inhalers of heroin and controls (genotype-wise, P = 0.006, allele-wise, P = 0.016) but not for injectors of heroin (genotype-wise, P = 0.81, allele-wise, P = 0.69). We also found that LD between all polymorphisms we examined in the gene was weak, possibly explaining why we see association of this polymorphism with heroin abuse but not with other markers in the gene. Overall our results indicates that the HTR2A, 5-HTT, DRD3 and GABA(A)gamma2 genes are not likely to be a major genetic risk factor for heroin abuse in this population, with the exception of possible association between nasal inhalation and DRD2 promoter - 141DeltaC polymorphism.

Adolescent↗
PubMed2002

[A linkage analysis of quantitative trait loci for familial schizophrenia on chromosome 1].

OBJECTIVE: To explore the molecular genetic relationship between chromosome 1 and quantitative trait loci for familial schizophrenia. METHODS: A series of assessment scales included positive and negative syndrome scale (PANSS), global assessment of functional scale (GAFS), premorbid schizoid and schizotypal traits scale (PSST), premorbid social adjustment scale (PSA) were applied to quantify the phenotypes of schizophrenia. Non-parametric linkage analysis of quantitative traits was conducted in 32 multiplex pedigrees with schizophrenia by using 29 microsatellite makers on chromosome 1. RESULTS: Haseman-Elston quantitative trait analysis detected a maximum Traditional H-E Lods of 1.73 and a maximum EH H-E Lods of 1.65 of negative symptoms (PANSS-N ) at 147.64 cM, which was overlapped to the positive region of 1q21-23 in qualitative linkage analysis. CONCLUSION: The results suggest there might be an independent quantitative trait locus of negative symptoms on 1q21-23 for familial schizophrenia.

Chromosomes, Human, Pair 1↗
PubMed2002

[Linkage analysis of susceptibility genes for familial schizophrenia on chromosome 1 in Chinese population].

OBJECTIVE: To explore the molecular genetic relationship between chromosome 1 and susceptibility genes for familial schizophrenia in Chinese population. METHODS: A genome scanning was conducted in 32 multiplex pedigrees from Chinese population by using 29 microsatellite markers on chromosome 1. RESULTS: Multipoint parametric analysis detected a maximum heterogenicity Lod of 1.70 at 262.52 cM under a recessive model; multipoint non-parametric analysis detected a maximum non-parameter linkage (NPL) of 1.71 (P=0.046) at 262.52 cM, then 1.37 (P=0.086) at 149.70 cM, corresponding to marker D1S206 and D1S425 respectively. CONCLUSION: These results give further supports to the presence of susceptibility genes on chromosome 1q for familial schizophrenia.

Adult↗
PubMedDate not supplied

Benchmarking physician performance, Part 1.

The performance of 16 primary care physicians in the same medical specialty and university clinic is compared using data envelopment analysis (DEA) efficiency scores. DEA is capable of modeling multiple criteria and automatically determines the relative weights of each performance measure. In this research, the performance measures include physician work relative value units (RVUs) as an input variable and patient satisfaction and total billable charges as the two output variables. The results provide insights into: 1. Who are the best-performing physicians? 2. Who are the underperforming physicians? 3. How can underperforming physicians improve? 4. What are the underperformers' performance targets? 5. How do you deal with full- and part-time physicians in a university setting? This research also provides a preliminary framework for how work measurement and DEA analysis can be used as a basis for a medical team or physician compensation system.

Benchmarking↗
PubMedDate not supplied

Benchmarking physician performance, part 2.

Part 1 of this article (January-February 2006) reviewed ways of measuring the work of physicians through methods such as data envelopment analysis (DEA) and relative value units (RVUs). These techniques provide insights into: 1. Who are the best-performing physicians? 2. Who are the underperforming physicians? 3. How can underperforming physicians improve? 4. What are the underperformers' performance targets? 5. How do you deal with full- and part-time physicians in a university setting? Part 2 compares the performance of 16 primary care physicians in the same medical specialty using DEA efficiency scores. DEA is capable of modeling multiple criteria and automatically determines the relative weights of each performance measure. This research also provides a preliminary framework for how work measurement and DEA can be used as a basis for a medical team or physician compensation system.

Benchmarking↗