Browsing by Author "Smith, Rebecca L."

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    Deriving a Measure of Social Recovery Capital From the Important People and Activities Instrument: Construction and Psychometric Properties
    (Oxford University Press, 2022) Francis, Meredith W.; Bourdon, Jessica L.; Chan, Grace; Dick, Danielle M.; Edenberg, Howard J.; Kamarajan, Chella; Kinreich, Sivan; Kramer, John; Kuo, Sally I-Chun; Pandey, Ashwini K.; Pandey, Gayathri; Smith, Rebecca L.; Bucholz, Kathleen K.; McCutcheon, Vivia V.; Psychiatry, School of Medicine
    Aim: This study presents a measure of Social Recovery Capital (SRC) derived from the Important People and Activities instrument (IPA). Methods: The sample comprised young adults who participated in the Collaborative Study on the Genetics of Alcoholism, a high-risk family study of alcohol use disorder (N = 2472). Exploratory and confirmatory factor analysis identified influential items and factor structure, adjusting for family relatedness. The final scale was tested for reliability and validity. Results: Factor analysis retained 10 items loading on three factors (Network Abstinence Behaviors, Basic Network Structure and Network Importance) that together explained 42% of the variance in SRC. The total model showed adequate fit (Comparative Fit Index = 0.95; Tucker Lewis Index = 0.93; Root Mean Square Error of Approximation = 0.06; Standardized Root Mean Squared Residual = 0.05) and acceptable reliability (α = 0.60; McDonald's ω = 0.73) and correlated with validation measures mostly in the weak to moderate range. Due to variable factor scores for reliability and validity, we only recommend using the total score. Conclusion: The SRC-IPA is a novel measure of SRC derived from the IPA that captures social network data and has applications in research and clinical work. Secondary data analyses using the SRC-IPA in studies that collected the IPA can further demonstrate the interaction of SRC with a wide variety of clinical indicators and demographic characteristics, making it a valuable addition to other measures of SRC.
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    Free Fatty Acids Rewire Cancer Metabolism in Obesity-Associated Breast Cancer via Estrogen Receptor and mTOR Signaling
    (AACR, 2019-05) Madak-Erdogan, Zeynep; Band, Shoham; Zhao, Yiru C.; Smith, Brandi P.; Kulkoyluoglu-Cotul, Eylem; Zuo, Qianying; Casiano, Ashlie Santaliz; Wrobel, Kinga; Rossi, Gianluigi; Smith, Rebecca L.; Kim, Sung Hoon; Katzenellenbogen, John A.; Johnson, Mariah L.; Patel, Meera; Marino, Natascia; Storniolo, Anna Maria V.; Flaws, Jodi A.; Medicine, School of Medicine
    Obesity is a risk factor for postmenopausal estrogen receptor alpha (ERα)-positive (ER+) breast cancer. Molecular mechanisms underlying factors from plasma that contribute to this risk and how these mechanisms affect ERα signaling have yet to be elucidated. To identify such mechanisms, we performed whole metabolite and protein profiling in plasma samples from women at high risk for breast cancer, which led us to focus on factors that were differentially present in plasma of obese versus nonobese postmenopausal women. These studies, combined with in vitro assays, identified free fatty acids (FFA) as circulating plasma factors that correlated with increased proliferation and aggressiveness in ER+ breast cancer cells. FFAs activated both the ERα and mTOR pathways and rewired metabolism in breast cancer cells. Pathway preferential estrogen-1 (PaPE-1), which targets ERα and mTOR signaling, was able to block changes induced by FFA and was more effective in the presence of FFA. Collectively, these data suggest a role for obesity-associated gene and metabolic rewiring in providing new targetable vulnerabilities for ER+ breast cancer in postmenopausal women. Furthermore, they provide a basis for preclinical and clinical trials where the impact of agents that target ERα and mTOR signaling cross-talk would be tested to prevent ER+ breast cancers in obese postmenopausal women.
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    Using a developmental perspective to examine the moderating effects of marriage on heavy episodic drinking in a young adult sample enriched for risk
    (Cambridge University Press, 2021) Cho, Seung Bin; Smith, Rebecca L.; Bucholz, Kathleen; Chan, Grace; Edenberg, Howard J.; Hesselbrock, Victor; Kramer, John; McCutcheon, Vivia V.; Nurnberger, John; Schuckit, Marc; Zang, Yong; Dick, Danielle M.; Salvatore, Jessica E.; Biochemistry and Molecular Biology, School of Medicine
    Many studies demonstrate that marriage protects against risky alcohol use and moderates genetic influences on alcohol outcomes; however, previous work has not considered these effects from a developmental perspective or in high-risk individuals. These represent important gaps, as it cannot be assumed that marriage has uniform effects across development or in high-risk samples. We took a longitudinal developmental approach to examine whether marital status was associated with heavy episodic drinking (HED), and whether marital status moderated polygenic influences on HED. Our sample included 937 individuals (53.25% female) from the Collaborative Study on the Genetics of Alcoholism who reported their HED and marital status biennially between the ages of 21 and 25. Polygenic risk scores (PRS) were derived from a genome-wide association study of alcohol consumption. Marital status was not associated with HED; however, we observed pathogenic gene-by-environment effects that changed across young adulthood. Among those who married young (age 21), individuals with higher PRS reported more HED; however, these effects decayed over time. The same pattern was found in supplementary analyses using parental history of alcohol use disorder as the index of genetic liability. Our findings indicate that early marriage may exacerbate risk for those with higher polygenic load.