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Biomedical subjects

Robert Kerwin

Publications and source records attributed to Robert Kerwin.

11 recordsLinked to original sources
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

Cortical serotonin 5-HT2A receptor binding and social communication in adults with Asperger's syndrome: an in vivo SPECT study.

OBJECTIVE: The cause of autistic spectrum disorder (i.e., autism and Asperger's syndrome) is unknown. The serotonergic (5-HT) system may be especially implicated. However, cortical 5-HT2A receptor density in adults with the disorder has not been examined, to the authors' knowledge. METHOD: The authors investigated cortical 5-HT2A receptor binding in eight adults with Asperger's syndrome and in 10 healthy comparison subjects with single photon emission computed tomography and the selective 5-HT2A receptor ligand 123I iodinated 4-amino-N-[1-[3-(4-fluorophenoxy)propyl]-4-methyl-4-piperidinyl]-5-iodo-2-methoxybenzamide (123I-5-I-R91150). RESULTS: People with Asperger's syndrome had a significant reduction in cortical 5-HT2A receptor binding in the total, anterior, and posterior cingulate; bilaterally in the frontal and superior temporal lobes; and in the left parietal lobe. Also, reduced receptor binding was significantly related to abnormal social communication. CONCLUSIONS: The authors' findings suggest that adults with Asperger's syndrome have abnormalities in cortical 5-HT2A receptor density and that this deficit may underlie some clinical symptoms.

Adult↗
PubMed2006

Author retraction.

Explore the source record for details and available documents.

Retraction Notice↗
PubMed2006

Discontinued drugs in 2005: schizophrenia drugs.

This paper is the third in a series discussing drugs dropped from development in 2005. Schizophrenia is particularly interesting with regard to pipeline discontinuation, and appears to be unique in this data set because the number of discontinuations far exceeds that for other neuropsychiatric conditions. If this is taken as a proxy for overall drug discovery activity, it represents a very large amount of activity across a wide range of big pharmaceutical corporations. It is also clear that many of the discontinued drugs have mechanisms of action that would make them theoretically suitable as treatments for schizophrenia. Why should so much activity be directed towards what many may consider an undeserving, relatively untreatable and relatively non-rehabilitatable group of patients? This is debated in this opinion piece.

Antipsychotic Agents↗
PubMed2004

Evidence that RNA editing modulates splice site selection in the 5-HT2C receptor gene.

Adenosine to inosine editing of mRNA from the human 5-HT2C receptor gene (HTR2C) occurs at five exonic positions (A-E) in a stable stem-loop that includes the normal 5' splice site of intron 5 and is flanked by two alternative splice sites. Using in vitro editing, we identified a novel editing site (F) located in the intronic part of the stem-loop and demonstrated editing at this site in human brain. We have shown that in cell culture, base substitutions to mimic editing at different combinations of the six sites profoundly affect relative splicing at the normal and the upstream alternative splice site, but splicing at the downstream alternative splice site was consistently rare. Editing combinations in different splice variants from human brain were determined and are consistent with the effects of editing on splicing observed in cell culture. As RNA editing usually occurs close to exon/intron boundaries, this is likely to be a general phenomenon and suggests an important novel role for RNA editing.

Aged↗
PubMed2003

Modelling the impact of clozapine on suicide in patients with treatment-resistant schizophrenia in the UK.

BACKGROUND: Schizophrenia is a major cause of suicide, and symptoms characteristic of treatment-resistant disease are strong risk factors. Clozapine reduces symptoms in 60% of such patients and significantly decreases the risk of suicide. AIMS: To model the impact of increased clozapine prescribing on lives saved and resource utilisation. METHOD: A model was built to compare current levels of clozapine prescribing with a scenario in which all suitable patients with treatment-resistant schizophrenia received clozapine. RESULTS: It was estimated that an average of 53 lives could be saved in the UK each year. If clozapine is cost-neutral, the cost per life-year saved is pound 5108. If clozapine achieves a 10% reduction in annual support costs, the net saving is pound 8.7 million per annum. An average of 167 acute beds would be freed each year. CONCLUSIONS: The use of clozapine in treatment-resistant schizophrenia saves lives, frees resources and is cost-effective.

Antipsychotic Agents↗
PubMed2002

Expression of Oct-6, a POU III domain transcription factor, in schizophrenia.

OBJECTIVE: Oct-6, a POU-III domain transcription factor, is expressed in embryonic stem cells and Schwann cells and in neuronal subpopulations during early mammalian development, but its relevance to disorders of cerebral development in humans is untested. This study evaluated the expression of Oct-6 in schizophrenia, a disorder that has been linked with neurodevelopmental abnormalities. METHOD: Immunohistochemistry was used to examine Oct-6 expression in the temporal lobe in postmortem tissue from 10 subjects with schizophrenia and 10 matched comparison subjects. Western blot analysis was used to study Oct-6 expression in the frontal and temporal cortex in tissue from an additional three schizophrenic and three matched comparison subjects and in the frontal lobe only in tissue from an additional 10 schizophrenic and 10 matched comparison subjects. RESULTS: Extensive Oct-6 immunoreactivity was present in the temporal lobe in all 10 schizophrenic subjects, while very little or no expression was found in the comparison subjects. In schizophrenic subjects, Oct-6 immunoreactivity was found in a subset of cells in the pyramidal cell layer of the hippocampus and in the granule cell layer of the dentate gyrus. Oct-6 staining was predominantly localized in the cytoplasm. Western blot analysis confirmed the presence of Oct-6 in the frontal and temporal cortex in schizophrenic subjects but not in comparison subjects. CONCLUSIONS: The presence of Oct-6 expression in the schizophrenic subjects but not in the comparison subjects suggests that Oct-6 may provide a marker for the neuropathology associated with schizophrenia. Further, it may provide a clue to the neurodevelopmental basis of the disease and could be a reliable means to examine the developmental brain abnormalities described in this disorder.

Adult↗
PubMed2002

Developments in the pharmacological treatment of schizophrenia.

Schizophrenia is, at once, a biological disease, a neuropsychological disorder and a dysfunction of social interactions. This presents clinicians with a series of problems with regards to therapy. In the first section of this article, some of the clinical challenges that face those attempting to develop new drugs, are summarised. Several potential pharmacological therapeutic targets that have been, and are continuing to be used, in the development of new antipsychotic drugs, are then considered. This is followed by an outline of the pharmacological and clinical profiles of some of the newer generation antipsychotics, as well as investigational drugs in the pipeline for schizophrenia. Finally, the implications of the introduction of these new drugs for the management of schizophrenia, are discussed.

Animals↗