The gut microbiota as a contributing factor to antipsychotic-induced weight gain and metabolic dysfunction

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dc.check.embargoformatE-thesis on CORA onlyen
dc.check.entireThesisEntire Thesis Restricted
dc.check.infoRestricted to everyone for one yearen
dc.check.opt-outNot applicableen
dc.check.reasonThis thesis is due for publication or the author is actively seeking to publish this materialen
dc.contributor.advisorO'Mahony, Siobhain M.en
dc.contributor.advisorDinan, Timothy G.en
dc.contributor.advisorCryan, John F.en
dc.contributor.authorDavey, Kieran
dc.date.accessioned2013-10-08T11:04:30Z
dc.date.available2014-10-09T04:00:05Z
dc.date.issued2013
dc.date.submitted2013
dc.description.abstractSchizophrenia represents one of the world’s most devastating illnesses due to its often lifelong course and debilitating nature. The treatment of schizophrenia has vastly improved over recent decades with the discovery of several antipsychotic compounds; however these drugs are not without adverse effects that must be addressed to maximize their therapeutic value. Newer, atypical, antipsychotics are associated with a compilation of serious metabolic side effects including weight gain, insulin resistance, fat deposition, glucose dysregulation and ensuing co-morbidities such as type II diabetes mellitus. The mechanisms underlying these side effects remain to be fully elucidated and adequate interventions are lacking. Further understanding of the factors that contribute these side effects is therefore required in order to develop effective adjunctive therapies and to potentially design antipsychotic drugs in the future with reduced impact on the metabolic health of patients. We investigated if the gut microbiota represented a novel mechanism contributing to the metabolic dysfunction associated with atypical antipsychotics. The gut microbiota comprises the bacteria that exist symbiotically within the gastrointestinal tract, and has been shown in recent years to be involved in several aspects of energy balance and metabolism. We have demonstrated that administration of certain antipsychotics in the rat results in an altered microbiota profile and, moreover, that the microbiota is required for the full scale of metabolic dysfunction to occur. We have further shown that specific antibiotics can attenuate certain aspects of olanzapine and risperidone–induced metabolic dysfunction, in particular fat deposition and adipose tissue inflammation. Mechanisms underlying this novel link appear to involve energy utilization via expression of lipogenic genes as well as reduced inflammatory tone. Taken together, these data indicate that the gut microbiota is an important factor involved in the myriad of metabolic complications associated with antipsychotic therapy. Furthermore, these data support the future investigation of microbial-based therapeutics for not only antipsychotic-induced weight gain but also for tackling the global obesity epidemic.en
dc.description.statusNot peer revieweden
dc.description.versionAccepted Version
dc.format.mimetypeapplication/pdfen
dc.identifier.citationDavey, K. 2013. The gut microbiota as a contributing factor to antipsychotic-induced weight gain and metabolic dysfunction. PhD Thesis, University College Cork.en
dc.identifier.endpage321
dc.identifier.urihttps://hdl.handle.net/10468/1243
dc.language.isoenen
dc.publisherUniversity College Corken
dc.rights© 2013. Kieran Daveyen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/en
dc.subjectMicrobiotaen
dc.subjectMetabolic syndromeen
dc.subjectOlanzapineen
dc.subjectAntipsychoticsen
dc.subject.lcshObesityen
dc.subject.lcshAntipsychotic drugsen
dc.subject.lcshSchizophrenia--Chemotherapyen
dc.subject.lcshGastrointestinal system--Microbiologyen
dc.thesis.opt-outfalse
dc.titleThe gut microbiota as a contributing factor to antipsychotic-induced weight gain and metabolic dysfunctionen
dc.typeDoctoral thesisen
dc.type.qualificationlevelDoctoralen
dc.type.qualificationnamePhD (Medicine and Health)en
ucc.workflow.supervisorsomahony@ucc.ie
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