{"id":{"repo_id":"uhi-uk","oai_identifier":"oai:pure.atira.dk:studenttheses/3e4585b2-4892-4bed-a673-41ab0d83f673"},"canonical_url":"https://search.dev.ndltd.org/etd/uhi-uk/oai:pure.atira.dk:studenttheses/3e4585b2-4892-4bed-a673-41ab0d83f673","repository":{"repo_id":"uhi-uk","name":"University of the Highlands and Islands","base_url":"https://pureadmin.uhi.ac.uk/ws/oai"},"display":{"title":"The impact of antipsychotic drugs on the expression of genes associated with obesity","abstract":"Schizophrenia is a severe and debilitating disorder, primarily treated with antipsychotic medication. Weight gain is a serious side-effect associated with most second generation antipsychotic drugs such as clozapine. The mechanism behind clozapine-induced weight gain remains poorly understood, but changes in eating behaviour and energy homeostasis may be involved. Recently, genome-wide association studies have identified a number of genetic
variants associated with obesity risk; however the effects of these risk variants on clozapineinduced weight gain have not been investigated. This doctoral thesis focused on the following research questions: (1) Does schizophrenia share a genetic link with obesity? (2) Can various antipsychotics alter the expression of obesity-related genes? (3) What is the initial signalling
event by which clozapine could induce a change in mRNA expression of the obesity-related genes?
The major findings from this work included that there was no demonstrable association between obesity-related variants and schizophrenia, and that low and intermediate doses of clozapine (0.125 μg/ml and 0.25 μg/ml) induced changes in mRNA expression of a panel of obesity-related genes in U937 cells. This effect was not observed in cells treated with haloperidol. However, the mRNA expression was also altered by treatment with olanzapine in most obesity-related genes tested but only in one gene when treated with risperidone. Treatment with 5-HT promoted an increase in mRNA expression of some obesity-related genes, which was similar to the treatment with 0.25 μg/ml clozapine although this effect was not apparent with a combination of clozapine and 5-HT. Changes in mRNA expression in clozapine-treated cells were likely mediated by the IP3 signalling pathway.
In conclusion, the mechanism behind weight gain in patients treated with either clozapine or olanzapine is multi-factorial: this study suggests that there may be an additional risk factor that could facilitate antipsychotic-induced weight gain: the altered the mRNA expression of obesityrelated genes.","abstract_html":"Schizophrenia is a severe and debilitating disorder, primarily treated with antipsychotic medication. Weight gain is a serious side-effect associated with most second generation antipsychotic drugs such as clozapine. The mechanism behind clozapine-induced weight gain remains poorly understood, but changes in eating behaviour and energy homeostasis may be involved. Recently, genome-wide association studies have identified a number of genetic<br/>variants associated with obesity risk; however the effects of these risk variants on clozapineinduced weight gain have not been investigated. This doctoral thesis focused on the following research questions: (1) Does schizophrenia share a genetic link with obesity? (2) Can various antipsychotics alter the expression of obesity-related genes? (3) What is the initial signalling<br/>event by which clozapine could induce a change in mRNA expression of the obesity-related genes?<br/>The major findings from this work included that there was no demonstrable association between obesity-related variants and schizophrenia, and that low and intermediate doses of clozapine (0.125 μg/ml and 0.25 μg/ml) induced changes in mRNA expression of a panel of obesity-related genes in U937 cells. This effect was not observed in cells treated with haloperidol. However, the mRNA expression was also altered by treatment with olanzapine in most obesity-related genes tested but only in one gene when treated with risperidone. Treatment with 5-HT promoted an increase in mRNA expression of some obesity-related genes, which was similar to the treatment with 0.25 μg/ml clozapine although this effect was not apparent with a combination of clozapine and 5-HT. Changes in mRNA expression in clozapine-treated cells were likely mediated by the IP3 signalling pathway.<br/>In conclusion, the mechanism behind weight gain in patients treated with either clozapine or olanzapine is multi-factorial: this study suggests that there may be an additional risk factor that could facilitate antipsychotic-induced weight gain: the altered the mRNA expression of obesityrelated genes.","abstract_has_math":false,"creators":["Mustard, Colette"],"institution":"University of Edinburgh","degree_name":"Doctor of Philosophy (awarded by OU/Aberdeen)","degree_level":"Doctoral Thesis","degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2016,"date_issued":"2016-7-31","date_published":"2016-7-31","updated_at":"2026-07-24T05:12:04Z","subjects":[],"languages":["eng"],"rights":[],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier","label":"Identifier","values":["oai:pure.atira.dk:studenttheses/3e4585b2-4892-4bed-a673-41ab0d83f673"],"render_values":[{"text":"oai:pure.atira.dk:studenttheses/3e4585b2-4892-4bed-a673-41ab0d83f673","href":null,"code":true}]}]},"links":{"outbound_url":"https://pure.uhi.ac.uk/en/studentTheses/3e4585b2-4892-4bed-a673-41ab0d83f673","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.sponsor","label":"Sponsor","values":["SAGB"]},{"key":"dc:creator","label":"Author","values":["Mustard, Colette"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2016-7-31"]},{"key":"dc:date.issued","label":"Date","values":["2016-7-31"]},{"key":"dc:publisher.department","label":"Dc Publisher Department","values":["Division of Biomedical Sciences"]},{"key":"dc:publisher.institution","label":"Dc Publisher Institution","values":["University of Edinburgh"]},{"key":"dc:relation.isreferencedby","label":"Dc Relation Isreferencedby","values":["https://pure.uhi.ac.uk/en/studentTheses/3e4585b2-4892-4bed-a673-41ab0d83f673"]},{"key":"dc:type","label":"Dc Type","values":["Thesis"]},{"key":"dc:type.qualificationlevel","label":"Dc Type Qualificationlevel","values":["Doctoral Thesis"]},{"key":"dc:type.qualificationname","label":"Dc Type Qualificationname","values":["Doctor of Philosophy (awarded by OU/Aberdeen)"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["eng"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["oai:pure.atira.dk:studenttheses/3e4585b2-4892-4bed-a673-41ab0d83f673","https://pure.uhi.ac.uk/en/studentTheses/3e4585b2-4892-4bed-a673-41ab0d83f673"]},{"key":"dc:identifier.uri","label":"Identifier URI","values":["https://pure.uhi.ac.uk/files/3084105/Colette_Mustard.pdf"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Schizophrenia is a severe and debilitating disorder, primarily treated with antipsychotic medication. Weight gain is a serious side-effect associated with most second generation antipsychotic drugs such as clozapine. The mechanism behind clozapine-induced weight gain remains poorly understood, but changes in eating behaviour and energy homeostasis may be involved. Recently, genome-wide association studies have identified a number of genetic
variants associated with obesity risk; however the effects of these risk variants on clozapineinduced weight gain have not been investigated. This doctoral thesis focused on the following research questions: (1) Does schizophrenia share a genetic link with obesity? (2) Can various antipsychotics alter the expression of obesity-related genes? (3) What is the initial signalling
event by which clozapine could induce a change in mRNA expression of the obesity-related genes?
The major findings from this work included that there was no demonstrable association between obesity-related variants and schizophrenia, and that low and intermediate doses of clozapine (0.125 μg/ml and 0.25 μg/ml) induced changes in mRNA expression of a panel of obesity-related genes in U937 cells. This effect was not observed in cells treated with haloperidol. However, the mRNA expression was also altered by treatment with olanzapine in most obesity-related genes tested but only in one gene when treated with risperidone. Treatment with 5-HT promoted an increase in mRNA expression of some obesity-related genes, which was similar to the treatment with 0.25 μg/ml clozapine although this effect was not apparent with a combination of clozapine and 5-HT. Changes in mRNA expression in clozapine-treated cells were likely mediated by the IP3 signalling pathway.
In conclusion, the mechanism behind weight gain in patients treated with either clozapine or olanzapine is multi-factorial: this study suggests that there may be an additional risk factor that could facilitate antipsychotic-induced weight gain: the altered the mRNA expression of obesityrelated genes."]},{"key":"dc:title","label":"Title","values":["The impact of antipsychotic drugs on the expression of genes associated with obesity"]}]}],"canonical_facts":{"dc:contributor.sponsor":["SAGB"],"dc:creator":["Mustard, Colette"],"dc:date":["2016-7-31"],"dc:date.issued":["2016-7-31"],"dc:description.abstract":["Schizophrenia is a severe and debilitating disorder, primarily treated with antipsychotic medication. Weight gain is a serious side-effect associated with most second generation antipsychotic drugs such as clozapine. The mechanism behind clozapine-induced weight gain remains poorly understood, but changes in eating behaviour and energy homeostasis may be involved. Recently, genome-wide association studies have identified a number of genetic
variants associated with obesity risk; however the effects of these risk variants on clozapineinduced weight gain have not been investigated. This doctoral thesis focused on the following research questions: (1) Does schizophrenia share a genetic link with obesity? (2) Can various antipsychotics alter the expression of obesity-related genes? (3) What is the initial signalling
event by which clozapine could induce a change in mRNA expression of the obesity-related genes?
The major findings from this work included that there was no demonstrable association between obesity-related variants and schizophrenia, and that low and intermediate doses of clozapine (0.125 μg/ml and 0.25 μg/ml) induced changes in mRNA expression of a panel of obesity-related genes in U937 cells. This effect was not observed in cells treated with haloperidol. However, the mRNA expression was also altered by treatment with olanzapine in most obesity-related genes tested but only in one gene when treated with risperidone. Treatment with 5-HT promoted an increase in mRNA expression of some obesity-related genes, which was similar to the treatment with 0.25 μg/ml clozapine although this effect was not apparent with a combination of clozapine and 5-HT. Changes in mRNA expression in clozapine-treated cells were likely mediated by the IP3 signalling pathway.
In conclusion, the mechanism behind weight gain in patients treated with either clozapine or olanzapine is multi-factorial: this study suggests that there may be an additional risk factor that could facilitate antipsychotic-induced weight gain: the altered the mRNA expression of obesityrelated genes."],"dc:identifier":["oai:pure.atira.dk:studenttheses/3e4585b2-4892-4bed-a673-41ab0d83f673","https://pure.uhi.ac.uk/en/studentTheses/3e4585b2-4892-4bed-a673-41ab0d83f673"],"dc:identifier.uri":["https://pure.uhi.ac.uk/files/3084105/Colette_Mustard.pdf"],"dc:language":["eng"],"dc:publisher.department":["Division of Biomedical Sciences"],"dc:publisher.institution":["University of Edinburgh"],"dc:relation.isreferencedby":["https://pure.uhi.ac.uk/en/studentTheses/3e4585b2-4892-4bed-a673-41ab0d83f673"],"dc:title":["The impact of antipsychotic drugs on the expression of genes associated with obesity"],"dc:type":["Thesis"],"dc:type.qualificationlevel":["Doctoral Thesis"],"dc:type.qualificationname":["Doctor of Philosophy (awarded by OU/Aberdeen)"]},"updated_at":"2026-07-24T05:12:04Z"}