Browsing by Author "Silvola, Rebecca"

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    Brain metabolic network covariance and aging in a mouse model of Alzheimer's disease
    (Wiley, 2024) Chumin, Evgeny J.; Burton, Charles P.; Silvola, Rebecca; Miner, Ethan W.; Persohn, Scott C.; Veronese, Mattia; Territo, Paul R.; Medicine, School of Medicine
    Introduction: Alzheimer's disease (AD), the leading cause of dementia worldwide, represents a human and financial impact for which few effective drugs exist to treat the disease. Advances in molecular imaging have enabled assessment of cerebral glycolytic metabolism, and network modeling of brain region have linked to alterations in metabolic activity to AD stage. Methods: We performed 18 F-FDG positron emission tomography (PET) imaging in 4-, 6-, and 12-month-old 5XFAD and littermate controls (WT) of both sexes and analyzed region data via brain metabolic covariance analysis. Results: The 5XFAD model mice showed age-related changes in glucose uptake relative to WT mice. Analysis of community structure of covariance networks was different across age and sex, with a disruption of metabolic coupling in the 5XFAD model. Discussion: The current study replicates clinical AD findings and indicates that metabolic network covariance modeling provides a translational tool to assess disease progression in AD models.
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    Comparing Newborn Outcomes After Prenatal Exposure to Individual Antidepressants: a retrospective cohort study
    (Wiley, 2021) Marks, Claire; Silvola, Rebecca; Teal, Evgennia; Quinney, Sara K,; Haas, David M.; Obstetrics and Gynecology, School of Medicine
    Objective: To compare associations between individual antidepressants and newborn outcomes. Design: Retrospective cohort study. Setting: Deliveries in a large, US medical system. Population: Women who received at least one antidepressant prescription 3 months prior to conception through delivery. Methods: Eligible women had maternal characteristics and newborn outcomes extracted from medical record data. Exposure was defined by the timing of the prescription during pregnancy. Main outcome measures: Newborn outcomes (any adaptation syndrome, neonatal intensive care unit (NICU) admission) were analyzed for each antidepressant and compared using standard statistics and multivariable regression compared to exposure to bupropion. Odds of outcomes based on timing of exposure were also explored. Results: A total of 3,694 women were analyzed. Rates of any adaptation syndrome (p < 0.001), NICU admission (p < 0.001), and transient tachypnea of newborn (TTN) (p = 0.006) were significantly different between drugs. Infants exposed to duloxetine had the highest rates of NICU admissions (39.6%) and adaptation syndromes (15.1%). Venlafaxine-exposed infants had the highest rates of TTN (18.2%). Controlling for maternal age, race, insurance, and gestational age at delivery, early pregnancy antidepressant exposure was associated with adaptation syndrome and NICU admission for both duloxetine (adjusted odds ratio (aOR) 2.31 [95% Confidence Interval (CI) 1.11-4.80] and aOR 2.47 [95% CI 1.40-4.34], respectively) and escitalopram (aOR 1.72 [95% CI 1.09-2.70] and aOR 1.64 [95% CI 1.21-2.22], respectively). Exposure in the third trimester was associated with any adaptation syndrome for citalopram, duloxetine, escitalopram, fluoxetine, sertraline, and venlafaxine and NICU admission for bupropion, citalopram, duloxetine, escitalopram, and fluoxetine. Conclusion: Duloxetine and escitalopram appear to have the strongest associations with any adaptation syndrome and NICU admission whereas bupropion and sertraline tended to have among the lowest risks of these outcomes. These results can help providers and patients discuss choice of individual antidepressant drugs during pregnancy.
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    Population Pharmacokinetics and Transfer of Gabapentin When Used as a Pain Adjunct for Cesarean Deliveries
    (Wiley, 2025) Silvola, Rebecca; O'Kane, Aislinn; Heathman, Michael; Marotta, Hannah; Trussel, Hayley; Ray, Bobbie; Dowden, Shelley; Masters, Andrea R.; Haas, David M.; Quinney, Sara K.; Medicine, School of Medicine
    Enhanced Recovery After Surgery (ERAS) protocols for cesarean deliveries (CDs) utilize multimodal pain management strategies that often include gabapentin. While gabapentin is excreted in breast milk, its pharmacokinetics in immediately postpartum lactating women are not known. This observational pharmacokinetic study (NCT05099484) enrolled 21 healthy singleton pregnant individuals, ≥ 18 years old, undergoing CD and planning to breastfeed. Participants received 300 mg oral gabapentin before CD and every 6 h for 48 h per hospital protocol. Serial maternal plasma and breast milk samples were collected over a single dosing interval. Gabapentin pharmacokinetics were assessed using two structurally distinct population pharmacokinetic (POPPK) models to describe transfer of drug into breast milk utilizing (A) milk-to-plasma ratio and (B) inter-compartmental rate constants. These models were then used to estimate exposure to breastfed infants. Postpartum gabapentin plasma concentrations fit a 1-compartment model that was adapted to include breast milk concentrations. The two POPPK models both estimated relative infant doses (RID0-48h) of gabapentin < 0.15% of maternal dose within the first 48 h postpartum. Infant daily dose (IDD) from 24 to 48 h was estimated to be 0.0137 (0.0058-0.0316) mg/kg/day and 0.0139 (0.00041-0.0469) mg/kg/day by models A and B, respectively. These findings indicate limited neonatal exposure to gabapentin administered as part of a postpartum enhanced recovery after surgery protocol.