Cognitive performance in elderly women: significance of the 19bp insertion/deletion polymorphism in the 5' flank of the dopamine beta-hydroxylase gene, educational level, body fat measures, serum triglyceride, alcohol consumption and age.

Background: Genetic and environmental factors influence cognitive aging. The gene encoding dopamine beta-hydroxylase (DBH) could be one such factor since this hydroxylase converts dopamine to norepinephrine both of which are involved in cognition regulation.

Objective: To assess the effect of the 19bp insertion/deletion polymorphism in the 5' flank of the DBH gene on cognitive performance in elderly women relative to other factors of cognitive aging.

GABA(A) receptor function is regulated by lipid bilayer elasticity.

Docosahexaenoic acid (DHA) and other polyunsaturated fatty acids (PUFAs) promote GABA(A) receptor [(3)H]-muscimol binding, and DHA increases the rate of GABA(A) receptor desensitization. Triton X-100, a structurally unrelated amphiphile, similarly promotes [(3)H]-muscimol binding. The mechanism(s) underlying these effects are poorly understood.

Diagnostic agreement of schizophrenia spectrum disorders among chronic patients with functional psychoses.

Background: To investigate whether diagnostic agreement across different diagnostic systems improves in a sample of chronic patients suffering from functional psychosis compared to first-admitted patients.

Sampling And Methods: Among 353 patients with a history of functional psychosis, a subset of 100 individuals (35 women and 65 men) were randomly sampled and assessed using the Operational Criteria Checklist for Psychotic Illness and Affective Illness (OPCRIT). Based on the OPCRIT diagnoses the subjects suffering from schizophrenia and schizophrenia spectrum disorders according to seven diagnostic systems were identified.

A closed-tube assay for genotyping of the 32-bp deletion polymorphism in the chemokine receptor 5 (CCR5) gene: dissociation analysis of amplified fragments of DNA.

We have developed a closed-tube assay for determination of the chemokine receptor type 5 (CCR5) 32-bp deletion allele, which protects against infections with HIV and modulates susceptibility to a variety of inflammatory diseases. This assay utilizes dissociation analysis of amplified products in the presence of Sybr Green I for allele discrimination. After having established robust conditions for the assay, we used it to genotype 590 unknown DNA samples.

Effects of the cannabinoid CB1 receptor agonist CP55,940 and antagonist SR141716A on d-amphetamine-induced behaviours in Cebus monkeys.

Several clinical studies have shown that alterations in the cannabinoid system in the brain may be associated with schizophrenia. Although evidence points towards an antipsychotic potential for cannabinoid antagonists, experimental studies have shown inconsistent behavioural effects of cannabinoid ligands within and across species. The aim of the present study was to explore these contradictory findings in a non-human primate model, predictive of antipsychotic efficacy in humans.

Association between the CCR5 32-bp deletion allele and late onset of schizophrenia.

Objective: The 32-bp deletion allele in chemokine receptor CCR5 has been associated with several immune-mediated diseases and might be implicated in schizophrenia as well.

Method: The authors genotyped DNA samples from 268 schizophrenia patients and 323 healthy subjects. Age at first admission to a psychiatric hospital department served as a measure of disease onset.

Identification and characterization of a tandem repeat in exon III of the dopamine receptor D4 (DRD4) gene in cetaceans.

A large number of mammalian species harbor a tandem repeat in exon III of the gene encoding dopamine receptor D4 (DRD4), a receptor associated with cognitive functions. In this study, a DRD4 gene exon III tandem repeat from the order Cetacea was identified and characterized. Included in our study were samples from 10 white-beaked dolphins (Lagenorhynchus albirostris), 10 harbor porpoises (Phocoena phocoena), eight sperm whales (Physeter macrocephalus), and five minke whales (Balaenoptera acutorostrata).

No significant association of the 5' end of neuregulin 1 and schizophrenia in a large Danish sample.

Neuregulin 1 has been implicated as a susceptibility gene in schizophrenia. Several research groups have reported association with the 5' end of the gene although no causative variant has been reported. We have investigated whether there is association with the 5' end of the gene in Danish schizophrenia patients.

Apolipoprotein D is associated with long-term outcome in patients with schizophrenia.

Accumulating evidence implicates deficiencies in apolipoprotein D (ApoD) function and arachidonic acid signaling in schizophrenic disorders. We addressed two hypotheses in relation to ApoD: first, polymorphisms in the ApoD gene confer susceptibility to or are markers of disease, and, second, genetic variation in the ApoD is associated with long-term clinical outcome to antipsychotic treatment. We genotyped two single-nucleotide polymorphisms in the ApoD gene in 343 chronic patients with schizophrenia spectrum disorders (ICD-10) and 346 control subjects of Danish origin.

Identification and characterization of tandem repeats in exon III of dopamine receptor D4 (DRD4) genes from different mammalian species.

In this study we have identified and characterized dopamine receptor D4 (DRD4) exon III tandem repeats in 33 public available nucleotide sequences from different mammalian species. We found that the tandem repeat in canids could be described in a novel and simple way, namely, as a structure composed of 15- and 12- bp modules. Tandem repeats composed of 18-bp modules were found in sequences from the horse, zebra, onager, and donkey, Asiatic bear, polar bear, common raccoon, dolphin, harbor porpoise, and domestic cat.

Reliability of clinical ICD-10 schizophrenia diagnoses.

Concern has been expressed as to the reliability of clinical ICD-10 diagnosis of schizophrenia. This study was designed to assess the diagnostic reliability of the clinical ICD-10 diagnosis of schizophrenia in a random sample of Danish in- and outpatients with a history of psychosis. A sample of 100 subjects was assessed using the operational criteria OPCRIT checklist for psychotic and affective illness.

Genotyping of the 19-bp insertion/deletion polymorphism in the 5' flank of beta-hydroxylase gene by dissociation analysis of allele-specific PCR products.

The 19-bp insertion/deletion polymorphism in the 5' flank of the dopamine beta-hydroxylase (DBH) gene has been associated with psychiatric disorders. We have developed a simple, reliable and inexpensive closed-tube assay for genotyping of this polymorphism based upon T(m) determination of amplified DNA fragments. Mistyping of heterozygote samples due to preferential allele amplification was prevented by use of an optimized concentration of Mg(2+), addition of dimethyl sulfoxide and annealing/extension at an appropriate temperature.

Serotonin transporter: evolution and impact of polymorphic transcriptional regulation.

The serotonin transporter (SERT) is the primary drug target in the current antidepressant therapy. A functional polymorphism in the 2nd intron of the 5HTT gene encoding the SERT has been identified and associated with susceptibility to affective disorders and treatment response to antidepressants. This study addresses the possible impact of the variable number of tandem repeats (VNTR) to behavior and disease by examining the evolutionary origin and mechanisms of differential transcriptional regulation of SERT.

The substituted (S)-3-phenylpiperidine (-)-OSU6162 reduces apomorphine- and amphetamine-induced behaviour in Cebus apella monkeys.

Low affinity dopamine (DA) D2 antagonists such as the substituted (S)-3-phenylpiperidine (-)-OSU6162 have been proposed to be putative antipsychotic agents not endowed with extrapyramidal side effects (EPS). In the present study we investigated the effects of (-)-OSU6162 on (-)-apomorphine and d-amphetamine-induced behaviours in EPS sensitised Cebus apella monkeys. (-)-OSU6162 was administered subcutaneously in doses of 1, 3, 6 and 9 mg/kg alone and in combination with (-)-apomorphine (0.

The effects of dopamine D3 agonists and antagonists in a nonhuman primate model of tardive dyskinesia.

Tardive dyskinesia (TD), a serious complication of antipsychotic dopamine (DA) antagonist treatment, has been hypothesised to develop due to a dominant DA D1 relative to DA D2 receptor function. Recent genetic and pharmacological studies implicate the DA D3 receptor in TD. The present study examined the role of the DA D3 receptor in relation to the DA D1/D2 imbalance hypothesis of TD in nonhuman primates.

Cebus apella, a nonhuman primate highly susceptible to neuroleptic side effects, carries the GLY9 dopamine receptor D3 associated with tardive dyskinesia in humans.

Tardive dyskinesia (TD) is a severe side effect of traditional neuroleptics affecting a considerable number of schizophrenic patients. Accumulating evidence suggests the existence of a genetic disposition to TD and other extra pyramidal symptoms (EPS) most strongly linked to a ser/gly polymorphism in position 9 of the D3 dopamine receptor gene (DRD3). The Cebus apella monkey is the favored animal model to study TD and other EPS because of its high susceptibility to side effects of neuroleptics.

Cholesterol-induced protein sorting: an analysis of energetic feasibility.

The mechanism(s) underlying the sorting of integral membrane proteins between the Golgi complex and the plasma membrane remain uncertain because no specific Golgi retention signal has been found. Moreover one can alter a protein's eventual localization simply by altering the length of its transmembrane domain (TMD). M.

The adenosine A2A receptor agonist CGS 21680 exhibits antipsychotic-like activity in Cebus apella monkeys.

The adenosine A2A receptor agonist CGS 21680 has shown effects similar to dopamine antagonists in behavioural assays in rats predictive for antipsychotic activity, without induction of extrapyramidal side-effects (EPS). In the present study, we examined whether this functional dopamine antagonism and lack of EPS in rodents could also be observed in non-human primates. We investigated the effects of CGS 21680 on behaviours induced by D-amphetamine and (-)-apomorphine in EPS-sensitized Cebus apella monkeys.

Antisense studies of brain GABAA receptors.

gamma-Aminobutyric acid (GABA) is the principal inhibitory neurotransmitter in the brain. The GABAA receptor complex, which is assumed to have a pentamer structure assembled from different polypeptide subunits, contains the binding sites for several clinically important compounds, e.g.

Altered response to intravenous thiopental and succinylcholine in acute amphetamine abuse.

Substance abuse has become increasingly prevalent: illegal drugs have profound and varied physiologic effects which create a large potential for anesthetic problems and complications (1). Amphetamine is a strong sympathomimetic and may therefore influence the course of anesthesia. We report the case of a patient with acute amphetamine abuse presenting difficulties during anesthesia.

2-Oxo-2H-Pyrimido[2,1-b]benzothiazoles inhibit brain benzodiazepine receptor binding in vitro.

2-Oxo-2H-pyrimido[2,1-b]benzothiazole derivatives were found to inhibit the in vitro binding of (3)H-Ro 15-1788 ((3)H-flumazenil) to rat cortical benzodiazepine receptors with IC(50) values in the range of 0.7-13 micromol/l. The most potent compound, 2-oxo-4-phenyl-2H-pyrimido[2,1-b]- benzothiazole showed a similar potency to inhibit (3)H-Ro 15-1788 binding to membrane preparations of rat brain cortex, cerebellum and hippocampus as well as to various subunit combinations of recombinant human gamma-aminobutyric acid(A)/benzodiazepine receptors.