The candidate, Dr. Christina Lessov-Schlaggar, seeks support for 5 years through this Mentored Research Scientist Development Award (K01) in order to (1) obtain training in functional neuroimaging to complement her training in psychiatric genetics of tobacco use etiology;(2) gain understanding of developmental cognitive neuroscience to enhance knowledge and guide current and future investigation of tobacco use etiology;and (3) improve statistical skills for longitudinal data analysis. This proposal will prepare the applicant to establish an independent research program to understand neural and cognitive mechanisms of addiction development using genetic and neuroimaging approaches. This goal will be achieved through (i) secondary data analysis of developmental smoking trajectories and their relationship to tobacco dependence in a genetically informative sample of twins, and (ii) functional neuroimaging pilot data collection in a subset of the same twin sample to examine brain activation differences in addiction-related regions between regular and non-regular smokers. The functional neuroimaging pilot study will employ a co-twin control design which allows investigation of the effects of regular smoking on neural processing, unconfounded by genetic and family background factors. Since smoking trajectory and neuroimaging data will be available from the same individuals, brain activation differences can be mapped onto differences in smoking trajectories, which will serve as one reference point for subject selection and study design for future R01 applications. This proposal describes a comprehensive and focused training program that includes formal coursework, supervised self-directed learning and hands-on training in one of the nation's leading academic institutions and under the guidance of leaders in the fields of functional neuroimaging (Dr. Deanna Barch, mentor;Dr. Steven Petersen, co-mentor), genetics of tobacco use etiology (Dr. Pamela Madden, co-mentor), and behavioral genetics (Dr. Andrew Heath, consultant).
Cigarette smoking is the single, most preventable cause of lung cancer and is a significant source of morbidity and mortality worldwide. Improved understanding of brain and cognitive mechanisms of tobacco dependence and its development will contribute to better, potentially individually-tailored, prevention, intervention, and treatment approaches.
|McAvoy, Mark; Mitra, Anish; Coalson, Rebecca S et al. (2016) Unmasking Language Lateralization in Human Brain Intrinsic Activity. Cereb Cortex 26:1733-46|
|McCutcheon, Vivia V; Luke, Douglas A; Lessov-Schlaggar, Christina N (2016) Reduced Social Network Drinking is Associated with Improved Response Inhibition in Women During Early Recovery from Alcohol Use Disorders: A Pilot Study. Alcohol Clin Exp Res 40:170-7|
|Conway, Charles R; Gebara, Marie Anne; Walker, Marie C et al. (2015) Clinical characteristics and management of treatment-resistant depression. J Clin Psychiatry 76:1569-70|
|Tandon, Mini; Lessov-Schlaggar, Christina N; Tillman, Rebecca et al. (2014) Secondhand Smoke Exposure and Severity of Attention-Deficit/Hyperactivity Disorder in Preschoolers: A Pilot Investigation. Scand J Child Adolesc Psychiatr Psychol 2:37-40|
|McCutcheon, Vivia V; Lessov-Schlaggar, Christina N; Steinley, Douglas et al. (2014) Social network drinking and family history contribute equally to first-onset alcohol dependence in high risk adults. Drug Alcohol Depend 141:145-8|
|Power, Jonathan D; Schlaggar, Bradley L; Lessov-Schlaggar, Christina N et al. (2013) Evidence for hubs in human functional brain networks. Neuron 79:798-813|
|Lessov-Schlaggar, Christina N; Lepore, Rebecca L; Kristjansson, Sean D et al. (2013) Functional neuroimaging study in identical twin pairs discordant for regular cigarette smoking. Addict Biol 18:98-108|
|Lessov-Schlaggar, Christina N; Kristjansson, Sean D; Bucholz, Kathleen K et al. (2012) Genetic influences on developmental smoking trajectories. Addiction 107:1696-704|
|Agrawal, A; Verweij, K J H; Gillespie, N A et al. (2012) The genetics of addiction-a translational perspective. Transl Psychiatry 2:e140|
|Kristjansson, Sean D; Agrawal, Arpana; Lessov-Schlaggar, Christina N et al. (2012) The relationship between rs3779084 in the dopa decarboxylase (DDC) gene and alcohol consumption is mediated by drinking motives in regular smokers. Alcohol Clin Exp Res 36:162-70|
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