Obesity is a profound public health issue and an even more alarming problem for patients with schizophrenia, who are obese at rates twice those observed in the general population. The use of certain neuroleptics to treat the symptoms of schizophrenia contributes greatly to weight gain in the illness. Olanzapine and clozapine, for example, can result in substantial weight gain while neuroleptics such as risperidone appear to cause modest weight gain. There is a relatively rich understanding of the molecular mechanisms of these drugs, yet the processes by which they cause metabolic side effects such as obesity are unknown. While imaging studies by our group and others have begun to improve our understanding of the neuronal processes involved in food intake behavior related to obesity in the general population, these mechanisms have not yet been studied in patients with schizophrenia. The overall goals of this proposal are to improve our understanding of the neuronal mechanisms by which neuroleptics contribute to obesity in schizophrenia and to determine whether an intervention such as exercise causes changes in neuronal response that would predict improved regulation of food intake behavior in schizophrenia. These goals will be addressed with two aims. First, we will determine (a) whether neuronal responses to a meal are altered and are related to food intake behaviors in obese compared to lean patients with schizophrenia and (b) whether neuroleptics that cause the most weight gain in patients are associated with greater alterations in neuronal responses related to food intake behavior compared to those associated with less weight gain. Second, this project will determine if a 12-week exercise intervention, as compared to diet, improves function of brain networks associated with food intake behavior in patients with schizophrenia. Understanding the potential mechanisms of dysregulated or altered food intake in patients with schizophrenia and the effect of neuroleptics will have a significant impact on the field and will elucidate possible mechanisms to help develop better, targeted therapeutic interventions for this population. These goals are in line with both the NIMH Strategic Objective to develop better interventions that incorporate the diverse needs of people with mental illnesses, and the Strategic Plan for NIH Obesity Research, which aims to develop more effective approaches to address the tremendous burden of obesity.

Public Health Relevance

Obesity is a profound public health concern and is an even more alarming problem for patients with schizophrenia, whose neuroleptic treatment leads to obesity rates twice those observed in the general population. This proposal investigates the neurobiology of how neuroleptics contribute to obesity in schizophrenia and evaluates whether an intervention such as exercise causes changes in neuronal response that would predict improved regulation of food intake behavior in schizophrenia.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
1R01MH102224-01A1
Application #
8756619
Study Section
Adult Psychopathology and Disorders of Aging Study Section (APDA)
Program Officer
Chavez, Mark
Project Start
2014-08-13
Project End
2019-07-31
Budget Start
2014-08-13
Budget End
2015-07-31
Support Year
1
Fiscal Year
2014
Total Cost
$387,500
Indirect Cost
$137,500
Name
University of Colorado Denver
Department
Psychiatry
Type
Schools of Medicine
DUNS #
041096314
City
Aurora
State
CO
Country
United States
Zip Code
80045
Legget, Kristina T; Cornier, Marc-Andre; Bessesen, Daniel H et al. (2018) Greater Reward-Related Neuronal Response to Hedonic Foods in Women Compared with Men. Obesity (Silver Spring) 26:362-367
Tregellas, Jason R; Smucny, Jason; Rojas, Donald C et al. (2018) Predicting academic career outcomes by predoctoral publication record. PeerJ 6:e5707
Smucny, Jason; Wylie, Korey P; Kronberg, Eugene et al. (2017) Nicotinic modulation of salience network connectivity and centrality in schizophrenia. J Psychiatr Res 89:85-96
Wylie, Korey P; Smucny, Jason; Legget, Kristina T et al. (2016) Targeting Functional Biomarkers in Schizophrenia with Neuroimaging. Curr Pharm Des 22:2117-23
Smucny, Jason; Olincy, Ann; Rojas, Donald C et al. (2016) Neuronal effects of nicotine during auditory selective attention in schizophrenia. Hum Brain Mapp 37:410-21
Norris, Scott A; Jinnah, H A; Espay, Alberto J et al. (2016) Clinical and demographic characteristics related to onset site and spread of cervical dystonia. Mov Disord 31:1874-1882
Sayer, R Drew; Amankwaah, Akua F; Tamer Jr, Gregory G et al. (2016) Effects of Dietary Protein and Fiber at Breakfast on Appetite, ad Libitum Energy Intake at Lunch, and Neural Responses to Visual Food Stimuli in Overweight Adults. Nutrients 8:
Smucny, Jason; Olincy, Ann; Tregellas, Jason R (2016) Nicotine restores functional connectivity of the ventral attention network in schizophrenia. Neuropharmacology 108:144-51
Berman, Brian D; Smucny, Jason; Wylie, Korey P et al. (2016) Levodopa modulates small-world architecture of functional brain networks in Parkinson's disease. Mov Disord 31:1676-1684
Regner, Michael F; Saenz, Naomi; Maharajh, Keeran et al. (2016) Top-Down Network Effective Connectivity in Abstinent Substance Dependent Individuals. PLoS One 11:e0164818

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