The origins of unpredictability in life outcome prediction tasks.

Why are some life outcomes difficult to predict? We investigated this question through in-depth qualitative interviews with 40 families sampled from a multidecade longitudinal study. Our sampling and interviewing process was informed by the earlier efforts of hundreds of researchers to predict life outcomes for participants in this study. The qualitative evidence we uncovered in these interviews combined with a mathematical decomposition of prediction error led us to create a conceptual framework. Our specific evidence and our more general framework suggest that unpredictability should be expected in many life outcome prediction tasks, even in the presence of complex algorithms and large datasets. Our work provides a foundation for future empirical and theoretical work on unpredictability in human lives.

Rewiring of the Host Cell Metabolome and Lipidome during Lytic Gammaherpesvirus Infection Is Essential for Infectious-Virus Production.

Oncogenic virus infections are estimated to cause ~15% of all cancers. Two prevalent human oncogenic viruses are members of the gammaherpesvirus family: Epstein-Barr virus (EBV) and Kaposi's sarcoma herpesvirus (KSHV). We use murine herpesvirus 68 (MHV-68), which shares significant homology with KSHV and EBV, as a model system to study gammaherpesvirus lytic replication. Viruses implement distinct metabolic programs to support their life cycle, such as increasing the supply of lipids, amino acids, and nucleotide materials necessary to replicate. Our data define the global changes in the host cell metabolome and lipidome during gammaherpesvirus lytic replication. Our metabolomics analysis found that MHV-68 lytic infection induces glycolysis, glutaminolysis, lipid metabolism, and nucleotide metabolism. We additionally observed an increase in glutamine consumption and glutamine dehydrogenase protein expression. While both glucose and glutamine starvation of host cells decreased viral titers, glutamine starvation led to a greater loss in virion production. Our lipidomics analysis revealed a peak in triacylglycerides early during infection and an increase in free fatty acids and diacylglyceride later in the viral life cycle. Furthermore, we observed an increase in the protein expression of multiple lipogenic enzymes during infection. Interestingly, pharmacological inhibitors of glycolysis or lipogenesis resulted in decreased infectious virus production. Taken together, these results illustrate the global alterations in host cell metabolism during lytic gammaherpesvirus infection, establish essential pathways for viral production, and recommend targeted mechanisms to block viral spread and treat viral induced tumors. IMPORTANCE Viruses are intracellular parasites which lack their own metabolism, so they must hijack host cell metabolic machinery in order to increase the production of energy, proteins, fats, and genetic material necessary to replicate. Using murine herpesvirus 68 (MHV-68) as a model system to understand how similar human gammaherpesviruses cause cancer, we profiled the metabolic changes that occur during lytic MHV-68 infection and replication. We found that MHV-68 infection of host cells increases glucose, glutamine, lipid, and nucleotide metabolic pathways. We also showed inhibition or starvation of glucose, glutamine, or lipid metabolic pathways results in an inhibition of virus production. Ultimately, targeting changes in host cell metabolism due to viral infection can be used to treat gammaherpesvirus-induced cancers and infections in humans.

Associations between middle childhood executive control aspects and adolescent substance use and externalizing and internalizing problems.

This study examines the degree to which two middle childhood executive control aspects, working memory and combined inhibitory control/flexible shifting, predict adolescent substance use and externalizing and internalizing problems. Participants were 301 children (ages 3-6 years; 48.2% male) recruited from a Midwestern city in the United States and followed into adolescence (ages 14-18 years). Working memory had a statistically significant unadjusted association with externalizing problems (r = -.30, p = .003) in a confirmatory factor analysis. Neither factor significantly predicted any of the adolescent outcomes in a structural equation model that adjusted for each EC aspect, sociodemographic covariates, and middle childhood externalizing and internalizing problems. Stronger prediction of EC aspects might not emerge until they become more fully differentiated later in development.

Exploring the Interaction Between Preschool Executive Control and Caregiver Emotion Socialization in Predicting Adolescent Weight Trajectories.

There is a critical need for research examining how neural vulnerabilities associated with obesity, including lower executive control, interact with family factors to impact weight trajectories across adolescence. Utilizing a longitudinal design, the present study investigated caregivers' emotion socialization practices as a moderator of the association between preschool executive control and adolescent body mass index (BMI) trajectories. Participants were 229 youth (Mage = 5.24, SD = 0.03; 47.2% assigned female at birth; 73.8% White, 3.9% Black, 0.4% Asian American, 21.8% multiracial; 12.7% Hispanic) enrolled in a longitudinal study. At preschool-age, participants completed performance-based executive control tasks, and their caregivers reported on their typical emotion-related socialization behaviors (i.e., supportive and nonsupportive responses to children's negative emotions). Participants returned for annual laboratory visits at ages 14 through 17, during which their height and weight were measured to calculate BMI. Although neither preschool executive control nor caregiver emotion-related socialization behaviors were directly associated with BMI growth in adolescence, supportive responses moderated the association between executive control and BMI trajectories. The expected negative association between lower preschool executive control and greater BMI growth was present at below average levels of supportive responses, suggesting that external regulation afforded by supportive responses might reduce risk for adolescent overweight and obesity among children with lower internal self-regulatory resources during preschool. Findings highlight the importance of efforts to bolster executive control early in development and targeted interventions to promote effective caregiver emotion socialization (i.e., more supportive responses) for youth with lower internal self-regulatory abilities to mitigate risk for overweight and obesity and promote health across childhood and adolescence.

Does preschool executive control mediate the impact of early environmental unpredictability and deprivation on the general factor of psychopathology a decade later?

BACKGROUND: Although deprivation has been consistently shown to increase risk for psychopathology through impaired executive control, the unique effects of other dimensions of early adversity, such as unpredictability, on executive control development are poorly understood. The current study evaluated whether deprivation and/or unpredictability early in life have unique effects on the general factor of psychopathology through impaired preschool executive control. METHODS: Participants included 312 children (51% female) oversampled for greater sociodemographic risk. Preschool executive control was measured using a battery of nine developmentally appropriate executive control tasks. Dimensions of adversity were measured with observational and caregiver assessments, and psychopathology was measured with caregiver and child reports. RESULTS: In separate models, both deprivation and unpredictability had significant indirect effects on the adolescent general factor of psychopathology through impaired preschool executive control. However, when both dimensions of adversity were included simultaneously, early life deprivation, but not unpredictability, was uniquely associated with the general factor of psychopathology in adolescence through impaired preschool executive control. CONCLUSIONS: Preschool executive control appears to be a transdiagnostic mechanism through which deprivation, but not unpredictability, increases risk for the general factor of psychopathology in adolescence. Results elucidate potential transdiagnostic targets for intervention efforts aimed at reducing the development and maintenance of psychopathology across the life span.

Preschool Executive Control, Temperament, and Adolescent Dietary Behaviors.

BACKGROUND: Child temperament styles characterized by increased emotionality or pleasure seeking may increase risk for less healthful eating patterns, while strong executive control (EC) may be protective. The interaction of these characteristics with longitudinal outcomes has not yet been examined. PURPOSE: The aim of this study was to examine the association of preschool temperament and EC, as well as their interaction with adolescent eating. METHODS: Preschoolers (N = 313) were recruited into a longitudinal study, with behavioral measurement of EC at age 5.25 years, temperament assessed multiple times across preschool, and eating outcomes assessed in adolescence (mean age = 15.34 years). RESULTS: Separate latent moderated structural equation models demonstrated that weaker EC was associated with eating less healthful foods, including high sugar foods, sugar-sweetened beverages (SSBs), and convenience foods (p < .05). In the moderation models, negative affectivity temperament was correlated with eating less healthful foods, high sugar foods, and SSBs (p < .05). Children lower in surgency/extraversion temperament were more likely to drink SSBs. There was an interaction between temperament and EC, such that children high in negative affectivity with weaker EC were particularly more likely to consume less healthful foods, high sugar foods, and SSBs (p < .05). There was no interaction of surgency with EC and food consumption. CONCLUSIONS: Child characteristics measured early in development were associated with later adolescent eating behaviors. Adequate EC could be necessary to counteract the drive toward eating associated with temperaments high in negative affectivity.

A preschool temperament style called Negative Affectivity, characterized by high levels of reactivity and negative emotion, predicted eating patterns a decade later. These children were more likely to eat less healthful foods and drink sugary drinks as adolescents. Strong executive function skills were important for redirecting toward healthful eating in children with Negative Affectivity.

Race and ethnic variation in college students' allostatic regulation of racism-related stress.

Racism-related stress is thought to contribute to widespread race/ethnic health inequities via negative emotion and allostatic stress process up-regulation. Although prior studies document race-related stress and health correlations, due to methodological and technical limitations, they have been unable to directly test the stress-reactivity hypothesis in situ. Guided by theories of constructed emotion and allostasis, we developed a protocol using wearable sensors and daily surveys that allowed us to operationalize and time-couple self-reported racism-related experiences, negative emotions, and an independent biosignal of emotional arousal. We used data from 100 diverse young adults at a predominantly White college campus to assess racism-related stress reactivity using electrodermal activity (EDA), a biosignal of sympathetic nervous system activity. We find that racism-related experiences predict both increased negative emotion risk and heightened EDA, consistent with the proposed allostatic model of health and disease. Specific patterns varied across race/ethnic groups. For example, discrimination and rumination were associated with negative emotion for African American students, but only interpersonal discrimination predicted increased arousal via EDA. The pattern of results was more general for Latinx students, for whom interpersonal discrimination, vicarious racism exposure, and rumination significantly modulated arousal. As with Latinx students, African students were particularly responsive to vicarious racism while 1.5 generation Black students were generally not responsive to racism-related experiences. Overall, these findings provide support for allostasis-based theories of mental and physical health via a naturalistic assessment of the emotional and sympathetic nervous system responding to real-life social experiences.

Early executive control buffers risk for adolescent psychopathology during the COVID-19 pandemic.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has had a global impact on youth mental health, and there is a critical need for research examining individual factors that contribute to increased psychopathology during the pandemic. The current study explored whether executive control (EC) abilities in early childhood interact with COVID-related stress to attenuate risk for adolescent psychopathology during the first 6 months of the pandemic. METHODS: Participants were 337 youth (49% female) living in a small midwestern city in the United States. Participants completed EC tasks when they were approximately 4.5 years old as part of a longitudinal study investigating cognitive development. At annual laboratory visits during adolescence and before the pandemic, participants (Mage = 14.57) reported on mental health symptoms. In July and August of 2020, participants (Mage = 16.57) reported on COVID-related stress and depression, anxiety, and trauma symptoms. RESULTS: COVID-related stress was associated with increased internalizing problems after controlling for prepandemic symptom levels. Further, the impact of COVID-related stress on adolescent internalizing problems was moderated by preschool EC, with higher levels of EC buffering the effects of COVID-related stress on adolescent internalizing problems. CONCLUSIONS: Findings highlight the importance of promoting EC early in development, as well as screening for EC deficits and implementing targeted intervention strategies across the lifespan to help reduce the impact of stress on adolescent internalizing problems.

Identifying gaps in parental support for families of children with hypoplastic left heart syndrome.

PURPOSE: The purpose of this study is to identify gaps in support for parents of children with Hypoplastic Left Heart Syndrome. DESIGN AND METHODS: Using a mixed-methods approach, the researchers first studied the parental and care team experience through interviews of Hypoplastic Left Heart Syndrome mothers and members of the inter-professional care team and then conducted an international survey of 690 Hypoplastic Left Heart Syndrome primary caregivers to validate the qualitative findings. RESULTS: Parental and care team interviews revealed three main gaps in parental support, including lack of open communication, unrealistic parental expectations, and unclear inter-professional team roles. Survey results found that parents whose children were diagnosed with Hypoplastic Left Heart Syndrome after birth indicated significant dissatisfaction with the care team's open communication and welcoming of feedback (p = 0.008). As parents progress through the stages of surgical intervention, they also indicate significant dissatisfaction with the care team's anticipation of parental emotional needs and provision of coping resources (p = 0.003). CONCLUSIONS: Parental support interventions should focus on providing resources to help parents cope, helping the care team model open communication, and welcoming feedback on the parental experience. PRACTICE IMPLICATIONS: Interventions should be piloted with parents who are in the later stages of the surgical intervention timeline or whose children were diagnosed after birth as they are the populations who perceived the least support within this study.

Model system identification of novel congenital heart disease gene candidates: focus on RPL13.

Genetics is a significant factor contributing to congenital heart disease (CHD), but our understanding of the genetic players and networks involved in CHD pathogenesis is limited. Here, we searched for de novo copy number variations (CNVs) in a cohort of 167 CHD patients to identify DNA segments containing potential pathogenic genes. Our search focused on new candidate disease genes within 19 deleted de novo CNVs, which did not cover known CHD genes. For this study, we developed an integrated high-throughput phenotypical platform to probe for defects in cardiogenesis and cardiac output in human induced pluripotent stem cell (iPSC)-derived multipotent cardiac progenitor (MCPs) cells and, in parallel, in the Drosophila in vivo heart model. Notably, knockdown (KD) in MCPs of RPL13, a ribosomal gene and SON, an RNA splicing cofactor, reduced proliferation and differentiation of cardiomyocytes, while increasing fibroblasts. In the fly, heart-specific RpL13 KD, predominantly at embryonic stages, resulted in a striking 'no heart' phenotype. KD of Son and Pdss2, among others, caused structural and functional defects, including reduced or abolished contractility, respectively. In summary, using a combination of human genetics and cardiac model systems, we identified new genes as candidates for causing human CHD, with particular emphasis on ribosomal genes, such as RPL13. This powerful, novel approach of combining cardiac phenotyping in human MCPs and in the in vivo Drosophila heart at high throughput will allow for testing large numbers of CHD candidates, based on patient genomic data, and for building upon existing genetic networks involved in heart development and disease.

Associations Between Preschool Sleep Problems and Observed Dimensions of Elementary Classroom Engagement.

Sleep has clear importance for academic success. However, most research in this area has focused on older children and adolescents and has used narrow measures of academic achievement, overlooking the importance of early sleep problems in shaping children's classroom behaviors that support academic success. Using a community sample (N = 276, 50% female), the current study examined associations between parent-reported preschool sleep problems (M age = 3.84, SD = 0.83) and three dimensions of classroom engagement coded during live classroom observations in the first grade (M age = 6.72, SD = 0.34). The moderating role of family socioeconomic status (SES) was also considered. A multivariate multilevel model found that more preschool sleep problems were associated with less focused engagement (defined as involvement in academic tasks, such as writing or asking questions), but more competing responses (defined as inappropriate or distracting behaviors). Preschool sleep problems were not associated with task management (defined as preparation for academic tasks, such as locating classroom materials). Although family SES did not moderate any of these associations, higher income-to-needs ratios in preschool were associated with more focused engagement and fewer competing responses. Findings highlight the role of early sleep problems in classroom behaviors that facilitate academic success. Targeting sleep problems prior to the school transition may serve as a useful approach to optimizing learning conditions during this key developmental period.

Natural underlying mtDNA heteroplasmy as a potential source of intra-person hiPSC variability.

Functional variability among human clones of induced pluripotent stem cells (hiPSCs) remains a limitation in assembling high-quality biorepositories. Beyond inter-person variability, the root cause of intra-person variability remains unknown. Mitochondria guide the required transition from oxidative to glycolytic metabolism in nuclear reprogramming. Moreover, mitochondria have their own genome (mitochondrial DNA [mtDNA]). Herein, we performed mtDNA next-generation sequencing (NGS) on 84 hiPSC clones derived from a cohort of 19 individuals, including mitochondrial and non-mitochondrial patients. The analysis of mtDNA variants showed that low levels of potentially pathogenic mutations in the original fibroblasts are revealed through nuclear reprogramming, generating mutant hiPSCs with a detrimental effect in their differentiated progeny. Specifically, hiPSC-derived cardiomyocytes with expanded mtDNA mutations non-related with any described human disease, showed impaired mitochondrial respiration, being a potential cause of intra-person hiPSC variability. We propose mtDNA NGS as a new selection criterion to ensure hiPSC quality for drug discovery and regenerative medicine.

Altered serotonergic circuitry in SSRI-resistant major depressive disorder patient-derived neurons.

Disrupted serotonergic neurotransmission has long been implicated in major depressive disorder (MDD), for which selective serotonin reuptake inhibitors (SSRIs) are the first line of treatment. However, a significant percentage of patients remain SSRI-resistant and it is unclear whether and how alterations in serotonergic neurons contribute to SSRI resistance in these patients. Induced pluripotent stem cells (iPSCs) facilitate the study of patient-specific neural subtypes that are typically inaccessible in living patients, enabling the discovery of disease-related phenotypes. In our study of a well-characterized cohort of over 800 MDD patients, we generated iPSCs and serotonergic neurons from three extreme SSRI-remitters (R) and SSRI-nonremitters (NR). We studied serotonin (5-HT) biochemistry and observed no significant differences in 5-HT release and reuptake or in genes related to 5-HT biochemistry. NR patient-derived serotonergic neurons exhibited altered neurite growth and morphology downstream of lowered expression of key Protocadherin alpha genes as compared to healthy controls and Rs. Furthermore, knockdown of Protocadherin alpha genes directly regulated iPSC-derived neurite length and morphology. Our results suggest that intrinsic differences in serotonergic neuron morphology and the resulting circuitry may contribute to SSRI resistance in MDD patients.

Serotonin-induced hyperactivity in SSRI-resistant major depressive disorder patient-derived neurons.

Selective serotonin reuptake inhibitors (SSRIs) are the most prescribed antidepressants. They regulate serotonergic neurotransmission, but it remains unclear how altered serotonergic neurotransmission may contribute to the SSRI resistance observed in approximately 30% of major depressive disorder (MDD) patients. Patient stratification based on pharmacological responsiveness and the use of patient-derived neurons may make possible the discovery of disease-relevant neural phenotypes. In our study from a large cohort of well-characterized MDD patients, we have generated induced pluripotent stem cells (iPSCs) from SSRI-remitters and SSRI-nonremitters. We studied serotonergic neurotransmission in patient forebrain neurons in vitro and observed that nonremitter patient-derived neurons displayed serotonin-induced hyperactivity downstream of upregulated excitatory serotonergic receptors, in contrast to what is seen in healthy and remitter patient-derived neurons. Our data suggest that postsynaptic forebrain hyperactivity downstream of SSRI treatment may play a role in SSRI resistance in MDD.

Associations between specific components of executive control and eating behaviors in adolescence: A study using objective and subjective measures.

A growing literature suggests that executive control (EC; also known as "executive functioning" or "EF") in adolescence may play an important role in the development of key health behaviors, including eating behaviors. However, existing literature has significant limitations in the conceptualization and measurement of EC. The current study aims to address these limitations by employing a multidimensional approach to conceptualizing and measuring adolescent EC, including both objective and subjective measures covering multiple components of EC, and examining links with specific eating behaviors. A community sample of adolescents (N = 208; mean age = 14.5 years) completed a battery of performance-based neuropsychological tasks assessing specific components of EC (i.e., working memory, inhibitory control, flexible shifting), a norm-referenced questionnaire covering problems with specific components of EC in daily life, and a measure assessing key eating behaviors (i.e., uncontrolled eating, emotional eating, cognitive restraint). Objectively-measured adolescent working memory was significantly and uniquely associated with cognitive restraint, with stronger working memory associated with less cognitive restraint. No other associations between performance-based EC tasks and eating behaviors were found. In contrast, using subjective reports of EC, problems with inhibitory control were associated with greater uncontrolled eating, and problems with flexible shifting were associated with greater emotional eating. The results suggest links between specific aspects of EC and specific eating behaviors in adolescence, as well as the potential importance of context for understanding the role of EC in eating behavior. Given evidence that EC is modifiable, the findings have potential implications for novel interventions addressing eating behaviors by targeting EC.

Addressing Variability and Heterogeneity of Induced Pluripotent Stem Cell-Derived Cardiomyocytes.

Induced pluripotent stem cells (iPSCs) offer great promise in the areas of disease modeling, basic research, drug development, and regenerative medicine. Much of their value comes from the fact that they can be used to create otherwise inaccessible cell types, such as cardiomyocytes, which are genetically matched to a patient or any other individual of interest. A consistent issue plaguing the iPSC platform, however, involves excessive variability exhibited in the differentiated products. This includes discrepancies in genetic, epigenetic, and transcriptional features, cell signalling, the cell types produced from cardiac differentiation, and cardiomyocyte functionality. These properties can result from both the somatic source cells and environmental conditions related to the derivation and handling of these cells. Understanding the potential sources of variability, along with determining which factors are most relevant to a given application, are essential in advancing iPSC-based technologies.

Loss of Ventricular Function After Bidirectional Cavopulmonary Connection: Who Is at Risk?

Decline of single ventricle systolic function after bidirectional cavopulmonary connection (BDCPC) is thought to be a transient phenomenon. We analyzed ventricular function after BDCPC according to ventricular morphology and correlated this evolution to long-term prognosis. A review from Mayo Clinic databases was performed. Visually estimated ejection fraction (EF) was reported from pre-BDCPC to pre-Fontan procedure. The last cardiovascular update was collected to assess long-term prognosis. A freedom from major cardiac event survival curve and a risk factor analysis were performed. 92 patients were included; 52 had left ventricle (LV) morphology and 40 had right ventricle (RV) morphology (28/40 had hypoplastic left heart syndrome (HLHS)). There were no significant differences in groups regarding BDCPC procedure or immediate post-operative outcome. EF showed a significant and relevant decrease from baseline to discharge in the HLHS group: 59 ± 4% to 49 ± 7% or - 9% (p < 0.01) vs. 58 ± 3% to 54 ± 6% or - 4% in the non-HLHS RV group (p = 0.04) and 61 ± 4% to 60 ± 4% or - 1% in the LV group (p = 0.14). Long-term recovery was the least in the HLHS group: EF prior to Fontan 54 ± 2% vs. 56 ± 6% and 60 ± 4%, respectively (p < 0.01). With a median follow-up of 8 years post-BDCPC, six patients had Fontan circulation failure, four died, and three had heart transplantation. EF less than 50% at hospital discharge after BDCPC was strongly correlated to these major cardiac events (HR 3.89; 95% Cl 1.04-14.52). Patients with HLHS are at great risk of ventricular dysfunction after BDCPC. This is not a transient phenomenon and contributes to worse prognosis.

Associations of Early Socio-familial Stress with Maladaptive and Adaptive Functioning in Middle Childhood: Roles of Executive Control and Foundational Cognitive Abilities.

This study examined whether cognitive processes in preschool, conceptualized as a unitary construct of executive control (EC) as well as foundational cognitive abilities (FCA), predict both maladaptive and adaptive functioning in middle childhood and mediate associations between early childhood socio-familial stress and those functional outcomes. Performance-based, multidimensional, and age-appropriate measures of EC and FCA were collected in a laboratory setting from 313 preschool-age children at age 5, along with questionnaire data from children and their parents on three dimensions of early socio-familial stress and parent smoking. Parent, teacher, and child self-report data on 285 of these children were obtained when they were in grade 3 or 4. Middle childhood data were used to create indices of maladaptive and adaptive functioning. A bi-factor structural equation modeling analysis captured distinct dimensions of preschool EC and FCA and was used to test the hypothesized pathways. EC had a statistically significant negative association with later maladaptive functioning. FCA, but not EC, served as a mediator in links between each type of family stressor and both maladaptive and adaptive functioning in middle childhood. Results suggest that EC may play a role in predicting maladaptation, whereas early childhood FCA may operate as an intervening variable in pathways from early family stressors to subsequent maladaptation as well as adaptation. Findings point to the need to address FCA by reducing early family stressors. Early interventions that enhance cognitive abilities may help reduce maladaptive and promote adaptive functioning later in childhood, thereby potentially preventing, in turn, later behavioral problems.

Executive Control in Early Childhood as an Antecedent of Adolescent Problem Behaviors: A Longitudinal Study with Performance-based Measures of Early Childhood Cognitive Processes.

Identifying childhood cognitive processes that predict adolescent problem behaviors can help guide understanding and prevention of these behaviors. In a community sample of 313 youth recruited in a small Midwestern city between 2006 and 2012 (49% male, 64% European American), executive control and foundational cognitive abilities were assessed at age 5 in a lab setting with performance-based measures. In adolescence, youth provided self-report of problem behaviors in surveys administered annually between ages 14 and 16. Executive control was negatively associated with externalizing behavior problems and adolescents getting in trouble at school, accounting for foundational cognitive abilities and family background covariates. Executive control had negative, but nonsignificant, associations with internalizing problems and substance use initiation. The findings point to deficits in executive control as a childhood risk factor for later problems and a potential target for preventive interventions.

Confirmatory factor analysis of the parental feeding style questionnaire with a preschool sample.

PURPOSE: Despite being widely used, there has not yet been a confirmatory factor analysis (CFA) on the English version of the Parental Feeding Style Questionnaire (PFSQ). Preschool is a critical time to assess parental feeding styles, and the PFSQ is one of the few measures that can be used with young children. As such, the current study conducted the first CFA on the PFSQ in an English-speaking sample in the United States to establish preliminary evidence of its factor structure. METHODS: Parents of preschoolers aged 3-5 years (N = 297; M = 33.47 years; 85.2% mothers) presenting to a pediatric dentistry office in the Midwest of the United States were recruited to participate in this cross-sectional study. Parents completed the PFSQ in the waiting room of the dental office. Robust maximum likelihood factor analyses were conducted on the PFSQ. RESULTS: The original four-factor model was not confirmed, but rather, results provided preliminary support for a five-factor solution: Control over Eating, Instrumental Feeding, Emotional Feeding, Encouragement of Variety, and Prompting of Eating, CFI = 0.91, SRMR = 0.06, RMSEA = 0.05. CONCLUSIONS: The PFSQ is a widely used measure for assessing parental feeding styles in young children. However, the CFA indicated that the originally proposed four-factor structure did not fit well. Certain modifications to the measure were necessary to improve model fit. A five-factor model fit better, and six items were removed, reducing the original 27-item scale to 21 items. LEVEL OF EVIDENCE: Level V, cross-sectional descriptive study.