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Item A One-year Longitudinal Study of the Stress, Sleep, and Parenting of Mothers of Toddlers(Elsevier, 2022) McQuillan, Maureen E.; Bates, John E.; Staples, Angela D.; Deater-Deckard, Kirby; Pediatrics, School of MedicineObjectives: The present study, building on cross-sectional research showing links between mothers' sleep, stress, and parenting, used a longitudinal design to consider (1) the temporal direction of links between mothers' sleep and stress, (2) whether mother sleep deficits predict change in parenting across time, and (3) whether mother sleep deficits mediate the inverse association between stress and positive parenting. Design: The study used repeated measures of stress, mother sleep, and positive parenting at toddler ages 30, 36, and 42 months. Setting: Data were collected at 2 sites, one in the Midwest and one in the East. Participants: Four hundred thirteen mother-toddler pairs were followed. Mothers were mostly married, college educated, and middle class, but there was also considerable variability between families. Measurements: Stress was measured via parenting hassles, CHAOS, and role overload scales. Mother sleep was measured via actigraphy. Positive parenting was observed during the bedtime routine and rated using the HOME scale and other items. Results: Mother stress and sleep were inextricably linked across toddlerhood, and worse sleep was predictive of less observed positive parenting, even when controlling for prior levels of stress and parenting. Conclusions: Improving mothers' sleep may be important in efforts to improve their parenting.Item A qualitative study of pain and related symptoms experienced by people with Ehlers-Danlos syndromes(Frontiers Media, 2024-01-03) Schubart, Jane R.; Mills, Susan E.; Francomano, Clair A.; Stuckey-Peyrot, Heather; Medical and Molecular Genetics, School of MedicineIntroduction: Individuals with Ehlers-Danlos syndromes (EDS) often have complex and multi-faceted symptoms across the lifespan. Pain and the related symptoms of fatigue and sleep disorders are common. The objective of this qualitative study was to understand how participants manage their pain and related symptoms. Methods: The design was a qualitative thematic content analysis. Twenty-eight interviews were conducted to collect data from individuals who were participants in a prior quantitative longitudinal study. A semi-structured interview guide was designed to focus on and understand the trajectory of pain, sleep, fatigue, and general function. The interview continued with questions about coping mechanisms and obstacles to maintaining a sense of well-being. Results: Symptoms reported by participants were widespread and often interwoven. Pain was universal and often resulted in fatigue and disordered sleep which impacted physical function. Most participants reported that their symptoms worsened over time. Participants reported a wide range of effective interventions and most reported developing self-care strategies to adapt to their disabilities/limitations. Solutions included complementary interventions discovered when conventional medicine was unsuccessful. Very few relied on a "system" of health care and instead developed their own strategies to adapt to their disabilities/limitations. Discussion: EDS symptoms are often debilitating, and their progression is unknown. For most participants, symptoms worsened over the time. Even though participants in our study, by experience, were self-reliant, the importance of knowledgeable medical providers to help guide self-care should be emphasized.Item Association of amyloid and cardiovascular risk with cognition: Findings from KBASE(Wiley, 2024) Chaudhuri, Soumilee; Dempsey, Desarae A.; Huang, Yen-Ning; Park, Tamina; Cao, Sha; Chumin, Evgeny J.; Craft, Hannah; Crane, Paul K.; Mukherjee, Shubhabrata; Choi, Seo-Eun; Scollard, Phoebe; Lee, Michael; Nakano, Connie; Mez, Jesse; Trittschuh, Emily H.; Klinedinst, Brandon S.; Hohman, Timothy J.; Lee, Jun-Young; Kang, Koung Mi; Sohn, Chul-Ho; Kim, Yu Kyeong; Yi, Dahyun; Byun, Min Soo; Risacher, Shannon L.; Nho, Kwangsik; Saykin, Andrew J.; Lee, Dong Young; KBASE Research Group; Radiology and Imaging Sciences, School of MedicineBackground: Limited research has explored the effect of cardiovascular risk and amyloid interplay on cognitive decline in East Asians. Methods: Vascular burden was quantified using Framingham's General Cardiovascular Risk Score (FRS) in 526 Korean Brain Aging Study (KBASE) participants. Cognitive differences in groups stratified by FRS and amyloid positivity were assessed at baseline and longitudinally. Results: Baseline analyses revealed that amyloid-negative (Aβ-) cognitively normal (CN) individuals with high FRS had lower cognition compared to Aβ- CN individuals with low FRS (p < 0.0001). Longitudinally, amyloid pathology predominantly drove cognitive decline, while FRS alone had negligible effects on cognition in CN and mild cognitive impairment (MCI) groups. Conclusion: Our findings indicate that managing vascular risk may be crucial in preserving cognition in Aβ- individuals early on and before the clinical manifestation of dementia. Within the CN and MCI groups, irrespective of FRS status, amyloid-positive individuals had worse cognitive performance than Aβ- individuals. Highlights: Vascular risk significantly affects cognition in amyloid-negative older Koreans. Amyloid-negative CN older adults with high vascular risk had lower baseline cognition. Amyloid pathology drives cognitive decline in CN and MCI, regardless of vascular risk. The study underscores the impact of vascular health on the AD disease spectrum.Item Changes over time in endorsement of 11 DSM-IV alcohol use disorder (AUD) criteria in young adults with persistent or recurrent AUD in The Collaborative Study on the Genetics of Alcoholism(Wiley, 2023) Schuckit, Marc A.; Smith, Tom L.; Danko, George; Tear, Jake; Hennies, Jessica; Mendoza, Lee Anne; Hesselbrock, Victor; Edenberg, Howard J.; Hesselbrock, Michie; Bucholz, Kathleen; Chan, Grace; Kuperman, Samuel; Francis, Meredith W.; Plawecki, Martin H.; Biochemistry and Molecular Biology, School of MedicineBackground: Endorsement of specific Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) alcohol use disorder (AUD) criteria have been shown to change significantly over time in men in their thirties who have persistent or recurrent AUD. However, few studies have documented whether the endorsement of AUD items changes over time in younger individuals or in women. We evaluated changes in the endorsement of AUD criteria in 377 men and women with persistent or recurrent AUD during their twenties. Methods: Information on AUD-item endorsement over time was available for 223 men and 154 women aged 20-25 with persistent or recurrent AUD in at least three interviews in the Collaborative Study on the Genetics of Alcoholism. The statistical significance of endorsement changes over time was evaluated using the related-sample Cochran's Q test for the full sample and for men and women separately. Additional analyses evaluated sex differences in the patterns of change. Results: In the full sample, the predominant pattern was for a significant increase in the rates of endorsement for six of the seven alcohol dependence criteria but not in the four abuse criteria. A similar pattern was seen within men, but women had significant changes in only three of the seven dependence criteria. Conclusions: Endorsement of the seven alcohol dependence criteria among individuals with persistent or recurrent AUD in their twenties generally increased, but few changes were observed in the rates of endorsement of the four abuse criteria. These results are discussed in terms of how they reflect on the nature of AUD and the DSM criteria.Item Dieting and Substance Use Among White and Black Adolescent Girls(Elsevier, 2021) Rowe, Alia T.; Khazvand, Shirin; Wu, Wei; Barnes-Najor, Jessica; Zapolski, Tamika C. B.; Psychology, School of ScienceObjective: Previous research has found an increasing co-occurrence of dieting and substance use behavior among adolescent girls. However, to date few studies have examined the temporal ordering of these behaviors. Further, limited research has been conducted to explore whether the pathways are similar among both White and Black girls. Method: For the current study 1580 girls (grade 6-11; 78.2% White; 21.8% Black) provided data on their dieting behavior and substance use. A cross-lagged panel design was used to examine the concurrent and prospective relationship between dieting behavior and substance use across one year, then by race. Results: Among the full sample of girls, there was a significant concurrent relationship. Additionally, dieting behavior predicted substance use one year later, but the inverse relationship was not found. For the stratified analysis, dieting behavior and substance use were not correlated among Black girls at either time point, however concurrent relationships were found for White girls. For the prospective pathways non-significant effects were found for both groups. Discussion: These findings provide support for a temporal relationship between dieting behavior and substance use, such that the former predicts risk for the latter. However, when examined by race, some pathways of the full sample were found for White girls, whereas Black girls did not report an association between study variables. Thus, future studies should consider the impact of race within risk pathways.Item Domain-specific effects of prenatal fluoride exposure on child IQ at 4, 5, and 6–12 years in the ELEMENT cohort(Elsevier, 2022) Goodman, Carly V.; Bashash, Morteza; Green, Rivka; Song, Peter; Peterson, Karen E.; Schnaas, Lourdes; Mercado-García, Adriana; Martínez-Medina, Sandra; Hernández-Avila, Mauricio; Martinez-Mier, Angeles; Téllez-Rojo, Martha M.; Hu, Howard; Till, Christine; Dental Public Health and Dental Informatics, School of DentistryObjective: Prenatal exposure to fluoride has been associated with adverse neurodevelopmental outcomes. However, the neuropsychological profile of fluoride's developmental neurotoxicity at low levels and the stability of this relationship across childhood has not been characterized. We investigated the longitudinal and domain specific effect of prenatal fluoride exposure on IQ among children ages 4, 5, and 6-12 years in the Early Life Exposures in Mexico to Environmental Toxicants (ELEMENT) cohort. Methods: We measured the average of maternal urinary fluoride at each trimester of pregnancy adjusted for creatinine (MUFCRE). Children were administered the McCarthy Scales of Children's Abilities at ages 4 (N = 386) and 5 (N = 308), and the Wechsler Abbreviated Scale of Intelligence at age 6-12 (N = 278). We used generalized estimating equation (GEE) models to estimate the population averaged effect of MUFCRE concentration on longitudinal General Cognitive Index (GCI)/Full-Scale IQ (FSIQ), Verbal IQ (VIQ), and Performance IQ (PIQ) scores (N = 348). We tested for possible interactions between MUFCRE and child sex as well as for MUFCRE and time point on children's IQ. All models controlled for relevant available covariates. Results: The mean/median MUFCRE concentration was 0.90/0.83 mg/L (SD = 0.39; IQR, 0.64-1.11 mg/L). A 0.5 mg/L increase in MUFCRE predicted an average 2.12-point decrease in GCI/FSIQ (95% CI: -3.49, -0.75) and 2.63-point decrease in PIQ (95% CI: -3.87, -1.40). MUFCRE was marginally associated with VIQ across time (B = -1.29, 95% CI: -2.60, 0.01). No interactions between MUFCRE and child sex or MUFCRE and time were observed. Conclusion: The negative association between prenatal fluoride exposure and longitudinal IQ was driven by decrements in non-verbal intelligence (i.e. PIQ), suggesting that visual-spatial and perceptual reasoning abilities may be more impacted by prenatal fluoride exposure as compared to verbal abilities.Item Examining psychological inflexibility as a mediator of postpartum depressive symptoms: A longitudinal observational study of perinatal depression(Elsevier, 2023) Thomas, Emily B. K.; Miller, Michelle L.; Grekin, Rebecca; O’Hara, Michael W.; Psychiatry, School of MedicineBackground: Depression is a common, serious complication during the postpartum period. Predictors of postpartum depression characterize who is at-risk for persistent symptoms. This study explored how psychological inflexibility affects depressive symptoms at 4 and 12 weeks postpartum. Methods: Participants receiving prenatal care at a medical center were recruited during the second trimester. Participants (n = 180) completed online assessments and diagnostic interviews during the third trimester (≥ 28 weeks gestation), and at 4-, 8-, and 12-weeks postpartum. Online assessments measured psychological inflexibility (PI) and depressive symptoms, while diagnostic interviews measured lifetime history of depression. Results: Mediation analysis examined pathways between 4-weeks postpartum depression, 8-weeks postpartum PI, and 12-weeks postpartum depression. Depressive symptoms at 4-weeks postpartum predicted PI at 8-weeks postpartum (β = 0.31, SE = 0.06, t(177) = 6.06, p < .001). Depressive symptoms at 4-weeks postpartum (β = 0.42, SE = 0.06, t(176) = 7.12, p < .001) and PI at 8-weeks postpartum (β = 0.32, SE = .08, t(176) = 4.09, p < .001) predicted depressive symptoms at 12-weeks postpartum. Depressive symptoms at 4-weeks, 8-week PI, and lifetime history of depression accounted for 42% of the variance in 12-week depressive symptoms (R2 = 0.42). The confidence interval of the indirect effect (0.04, 0.18) did not include zero, indicating significant mediation by PI. Conclusions: PI mediated the relation between 4- and 12-weeks postpartum depressive symptoms when controlling for lifetime history of depression. Psychological inflexibility is a transdiagnostic target for future prevention and intervention research during the postpartum period.Item The Genetic Architecture of Alzheimer's Disease Endophenotypes(2022-05) Jacobson, Tanner Young; Saykin, Andrew J.; Nho, Kwangsik; Foroud, Tatiana; Zhang, Chi; Cao, ShaAlzheimer’s Disease (AD) is one of the most common forms of dementia and is known to have a strong genetic component, but known genetic loci do not fully account for the observed genetic heritability of late onset AD. This genetic complexity is further complicated by disease heterogeneity, with non-uniform presentation and progression of AD neuropathology. Endophenotypes lie upstream of observed AD clinical outcomes and downstream of genetic contributors, allowing for a biological understanding of genetic effects. Understanding the genetic architecture of AD endophenotypes can aid in breaking down AD genetic complexity and heterogeneity. In this study we utilized a variety of models to evaluate the genetic contributors to pathological change and heterogeneity in the top markers of AD pathology: amyloid, tau, neurodegeneration, and cerebrovascular (A/T/N/V framework). Additional composite quantitative measures of cognitive performance were used to relate to downstream AD presentation. These biomarkers allow the investigation of genetic effects contributing to the disease over the stages of disease progression from amyloid deposition to neurofibrillary tangle formation, disruption of metabolism, brain atrophy, and finally to clinical outcomes. First, we performed genome-wide association studies (GWAS) for AD endophenotypes at baseline using a cross-sectional regression model. This method identified sixteen novel or replicated loci, with six (SRSF10, MAPT, XKR3, KIAA1671, ZNF826P, and LOC100507506) associated across multiple A/T/N biomarkers. Cross-sectional data was further utilized to identify three genetic loci (BACH2, EP300, PACRG-AS1) that showed disease stage specific interaction effects. We built upon those results by performing a longitudinal association analysis with linear-mixed effects modeling. Gene enrichment analysis of these results identified 19 significant genetic regions associated with linear longitudinal change in AD endophenotypes. To further break down longitudinal heterogeneity, a latent class mixed model approach was utilized to identify subgroups of longitudinal progression within cognitive and MRI measures, with 16 genetic loci associated with membership in different classes. The genetic patterns of these subgroups show biological relevance in AD. The methods and results from this study provide insight into the complex genetic architecture of AD endophenotypes and a foundation to build upon for future studies into AD genetic architecture.Item Geographical Landscape and Transmission Dynamics of SARS-CoV-2 Variants Across India: A Longitudinal Perspective(Frontiers Media, 2021-12-17) Jha, Neha; Hall, Dwight; Kanakan, Akshay; Mehta, Priyanka; Maurya, Ranjeet; Mir, Quoseena; Gill, Hunter Mathias; Janga, Sarath Chandra; Pandey, Rajesh; Biomedical Engineering and Informatics, Luddy School of Informatics, Computing, and EngineeringGlobally, SARS-CoV-2 has moved from one tide to another with ebbs in between. Genomic surveillance has greatly aided the detection and tracking of the virus and the identification of the variants of concern (VOC). The knowledge and understanding from genomic surveillance is important for a populous country like India for public health and healthcare officials for advance planning. An integrative analysis of the publicly available datasets in GISAID from India reveals the differential distribution of clades, lineages, gender, and age over a year (Apr 2020–Mar 2021). The significant insights include the early evidence towards B.1.617 and B.1.1.7 lineages in the specific states of India. Pan-India longitudinal data highlighted that B.1.36* was the predominant clade in India until January–February 2021 after which it has gradually been replaced by the B.1.617.1 lineage, from December 2020 onward. Regional analysis of the spread of SARS-CoV-2 indicated that B.1.617.3 was first seen in India in the month of October in the state of Maharashtra, while the now most prevalent strain B.1.617.2 was first seen in Bihar and subsequently spread to the states of Maharashtra, Gujarat, and West Bengal. To enable a real time understanding of the transmission and evolution of the SARS-CoV-2 genomes, we built a transmission map available on https://covid19-indiana.soic.iupui.edu/India/EmergingLineages/April2020/to/March2021. Based on our analysis, the rate estimate for divergence in our dataset was 9.48 e-4 substitutions per site/year for SARS-CoV-2. This would enable pandemic preparedness with the addition of future sequencing data from India available in the public repositories for tracking and monitoring the VOCs and variants of interest (VOI). This would help aid decision making from the public health perspective.Item Heterotypic Continuity of Inhibitory Control in Early Childhood: Evidence from Four Widely Used Measures(American Psychological Association, 2021) Petersen, Isaac T.; Bates, John E.; McQuillan, Maureen E.; Hoyniak, Caroline P.; Staples, Angela D.; Rudasill, Kathleen M.; Molfese, Dennis L.; Molfese, Victoria J.; Pediatrics, School of MedicineInhibitory control has been widely studied in association with social and academic adjustment. However, prior studies have generally overlooked the potential heterotypic continuity of inhibitory control and how this could affect assessment and understanding of its development. In the present study, we systematically considered heterotypic continuity in four well-established measures of inhibitory control, testing two competing hypotheses: (1) the manifestation of inhibitory control coheres within and across time in consistent, relatively simple ways, consistent with homotypic continuity. Alternatively, (2) with developmental growth, inhibitory control manifests in more complex ways with changes across development, consistent with heterotypic continuity. We also explored differences in inhibitory control as a function of the child’s sex, language ability, and the family’s socioeconomic status. Children (N = 513) were studied longitudinally at 30, 36, and 42 months of age. Changes in the patterns of associations within and among inhibitory control measures across ages suggests that the measures’ meanings change with age, the construct manifests differently across development, and therefore, that the construct shows heterotypic continuity. We argue that the heterotypic continuity of inhibitory control motivates the use of different combinations of inhibitory control indexes at different points in development in future research to improve validity. Confirmatory factors and growth curves also suggest that individual differences in inhibitory control endure, with convergence among inhibitory control measures by 36 months of age.
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