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We introduce an innovative, data-driven topological data analysis (TDA) technique for estimating the state spaces of dynamically changing functional human brain networks at rest. Our method utilizes the Wasserstein distance to measure topological differences, enabling the clustering of brain networks into distinct topological states. This technique outperforms the commonly used k-means clustering in identifying brain network state spaces by effectively incorporating the temporal dynamics of the data without the need for explicit model specification. We further investigate the genetic underpinnings of these topological features using a twin study design, examining the heritability of such state changes. Our findings suggest that the topology of brain networks, particularly in their dynamic state changes, may hold significant hidden genetic information., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Chung et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: The aim of this study was to determine the number of patients undergoing large loop excision of the transformation zone (LLETZ), for biopsy-confirmed high-grade squamous intraepithelial lesions (HSIL), where the original cervical screening test (CST) reported oncogenic human papillomavirus (HPV) and negative liquid-based cytology (LBC). This reflects the number of patients where a LLETZ procedure would not have occurred under the previous guideline., Methods: Retrospective observational chart review of all patients (n = 477) who underwent LLETZ procedure in a single tertiary unit over a 36-month period. Prevalence of negative histopathology, positive margins, incidental cervical cancer, and accuracy of HSIL identification at colposcopy were measured. Diagnostic accuracy of HSIL diagnosis from initial colposcopic impression was calculated; factors influencing accuracy were evaluated using multivariable logistic regression analysis. There were no comparators., Results: Of 477 LLETZs, 5.9% (n = 28) were for oncogenic HPV and normal LBC on referral CST. Demographics between the "study" (oncogenic HPV and normal LBC on referral CST) and the "standard" group were similar, except the study group was less likely to be using contraception (25% vs 47%, p = .023). In the study group, initial colposcopic cervical biopsy confirmed HSIL in 91.6% (n = 27) and low-grade squamous intraepithelial lesions in 3.6% (n = 1). Histopathological analysis of LLETZ specimens confirmed HSIL in 20 patients (71.4%) and low-grade squamous intraepithelial lesions in 2 (7.1%). No microinvasion was detected., Conclusions: The renewed National Cervical Screening Programme (NCSP), is detecting more "at risk" patients, predicted to lead to a further reduction in incidence of cervical cancer in adequately screened patients., Competing Interests: The authors have declared they have no conflicts of interest., (Copyright © 2023, ASCCP.)

We examine neural correlates of discrete expressions of negative emotionality in infants to determine whether the microstructure of white matter tracts at 1 month of age foreshadows the expression of specific negative emotions later in infancy. Infants (n = 103) underwent neuroimaging at 1-month, and mothers reported on infant fear, sadness, and anger at 6, 12, and 18 months using the Infant Behavior Questionnaire-Revised. Levels and developmental change in fear, sadness, and anger were estimated from mother reports. Relations between MRI and infant emotion indicated that 1-month white matter microstructure was differentially associated with level and change in infant fear, but not anger or sadness, in the left stria terminalis (p < 0.05, corrected), a tract that connects frontal and tempo-parietal regions and has been implicated in emerging psychopathology in adults. More relaxed constraints on significance (p < 0.10, corrected) revealed that fear was associated with lower white matter microstructure bilaterally in the inferior portion of the stria terminalis and regions within the sagittal stratum. Results suggest the neurobehavioral uniqueness of fear as early as 1 month of age in regions that are associated with potential longer-term outcomes. This work highlights the early neural precursors of fearfulness, adding to literature explaining the psychobiological accounts of affective development. HIGHLIGHTS: Expressions of infant fear and anger, but not sadness, increase from 6 to 18 months of age. Early neural architecture in the stria terminalis is related to higher initial levels and increasing fear in infancy. After accounting for fear, anger and sadness do not appear to be associated with differences in early white matter microstructure. This work identifies early neural precursors of fearfulness as early as 1-month of age., (© 2022 The Authors. Developmental Science published by John Wiley & Sons Ltd.)

Background and Purpose: Incidental findings are discovered in neuroimaging research, ranging from trivial to life-threatening. We describe the prevalence and characteristics of incidental findings from 16,400 research brain MRIs, comparing spontaneous detection by nonradiology scanning staff versus formal neuroradiologist interpretation., Materials and Methods: We prospectively collected 16,400 brain MRIs (7782 males, 8618 females; younger than 1 to 94 years of age; median age, 38 years) under an institutional review board directive intended to identify clinically relevant incidental findings. The study population included 13,150 presumed healthy volunteers and 3250 individuals with known neurologic diagnoses. Scanning staff were asked to flag concerning imaging findings seen during the scan session, and neuroradiologists produced structured reports after reviewing every scan., Results: Neuroradiologists reported 13,593/16,400 (83%) scans as having normal findings, 2193/16,400 (13.3%) with abnormal findings without follow-up recommended, and 614/16,400 (3.7%) with "abnormal findings with follow-up recommended." The most common abnormalities prompting follow-up were vascular (263/614, 43%), neoplastic (130/614, 21%), and congenital (92/614, 15%). Volunteers older than 65 years of age were significantly more likely to have scans with abnormal findings ( P  < .001); however, among all volunteers with incidental findings, those younger than 65 years of age were more likely to be recommended for follow-up. Nonradiologists flagged <1% of MRIs containing at least 1 abnormality reported by the neuroradiologists to be concerning enough to warrant further evaluation., Conclusions: Four percent of individuals who undergo research brain MRIs have an incidental, potentially clinically significant finding. Routine neuroradiologist review of all scans yields a much higher rate of significant lesion detection than selective referral from nonradiologists who perform the examinations. Workflow and scan review processes need to be carefully considered when designing research protocols., (© 2023 by American Journal of Neuroradiology.)

An enduring issue in the study of mental health is identifying developmental processes that explain how childhood characteristics progress to maladaptive forms. We examine the role that behavioral inhibition (BI) has on social anxiety (SA) during adolescence in 868 families of twins assessed at ages 8, 13, and 15 years. Multimodal assessments of BI and SA were completed at each phase, with additional measures (e.g., parenting stress) for parents and twins. Analyses were conducted in several steps: first, we used a cross-lagged panel model to demonstrate bidirectional paths between BI and SA; second a biometric Cholesky decomposition showed that both genetic and environmental influences on childhood BI also affect adolescent SA; next, multilevel phenotypic models tested moderation effects between BI and SA. We tested seven potential moderators of the BI to SA prediction in individual models and included only those that emerged as significant in a final conditional model examining predictors of SA. Though several main effects emerged as significant, only parenting stress had a significant interaction with BI to predict SA, highlighting the importance of environmental moderators in models examining temperamental effects on later psychological symptoms. This comprehensive assessment continues to build the prototype for such developmental psychopathology models.

Introduction: Subject head motion is an ongoing challenge in functional magnetic resonance imaging, particularly in the estimation of functional connectivity. Infants (1-month old) scanned during nonsedated sleep often have occasional but large movements of several millimeters separated by periods with relatively little movement. This results in residual signal changes even after image realignment and can distort estimates of functional connectivity. A new motion correction technique, JumpCor, is introduced to reduce the effects of this motion and compared to other existing techniques. Methods: Different approaches for reducing residual motion artifacts after image realignment were compared both in actual and simulated data: JumpCor, regressing out the estimated subject motion, and regressing out the average white matter, cerebrospinal fluid (CSF), and global signals and their temporal derivatives. Results: Motion-related signal changes resulting from infrequent large motion were significantly reduced both by regressing out the estimated motion parameters and by JumpCor. Furthermore, JumpCor significantly reduced artifacts and improved the quality of functional connectivity estimates when combined with typical preprocessing approaches. Discussion: Motion-related signal changes resulting from occasional large motion can be effectively corrected using JumpCor and to a certain extent also by regressing out the estimated motion. This technique should reduce the data loss in studies where participants exhibit this type of motion, such as sleeping infants.

Temperament involves stable behavioral and emotional tendencies that differ between individuals, which can be first observed in infancy or early childhood and relate to behavior in many contexts and over many years. 1 One of the most rigorously characterized temperament classifications relates to the tendency of individuals to avoid the unfamiliar and to withdraw from unfamiliar people, objects, and unexpected events. This temperament is referred to as behavioral inhibition or inhibited temperament (IT). 2 IT is a moderately heritable trait 1 that can be measured in multiple species. 3 In humans, levels of IT can be quantified from the first year of life through direct behavioral observations or reports by caregivers or teachers. Similar approaches as well as self-report questionnaires on current and/or retrospective levels of IT 1 can be used later in life., (Copyright © 2022 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.)

Person-centered typologies identified with latent profile analysis can clarify patterns of chronic and acute risk factors for suicidal ideation. We derived five profiles of individuals using cognitive, behavioral, and familial factors relating to suicidal ideation risk factors. Participants (n = 1,142) were assessed at age 8 using the Laboratory Temperament Assessment Battery and mother-reported parenting measures and at age 14 using interviews about clinical symptoms and suicidal ideation. The best-fitting model included five profiles: typical, elevated adolescent symptomology, mildly elevated typical, low childhood persistence, and very low childhood persistence/mixed symptoms. Participants in the elevated adolescent symptomology and very low childhood persistence/mixed symptoms profiles were 2.6 and 5.3 times more likely to report suicidal ideation compared with the typical profile. Overall, our results underscore how using a person-centered pattern recognition approach and incorporating facets of childhood behavior may enhance conceptualizations of adolescent suicidal ideation risk., Competing Interests: The authors have declared that no competing interests exist.

We use the highly structured Laboratory-Temperament Assessment Battery to measure behaviors that map onto the Research Domain Criteria (RDoC) positive and negative valence systems. Using a birth record-based sample (N = 1374 individual twins; mean age 7.7 years), we created composites of observed behavior reflecting the RDoC constructs Reward Responsiveness, Frustrative Nonreward, Loss, and Fear. Next, we related the RDoC constructs concurrently and longitudinally to problem behaviors, measured using parent-report on the Health Behavior Questionnaire and symptom counts from the Diagnostic Interview Schedule for Children, Version IV (DISC-IV; reflecting DSM-IV). The four pediatric RDoC positive and negative valence system measures, especially Reward Responsiveness, Frustrative Nonreward, and Loss, were heritable and modestly but plausibly related to traditional DSM-based measures in a transdiagnostic manner. The modest predictions from RDoC measures to DSM-based measures were largely genetically mediated, although relationships with aggressive and oppositional behaviors were also influenced by common environmental factors. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Quantitative neuroimaging studies in twin samples can investigate genetic contributions to brain structure and microstructure. Diffusion tensor imaging (DTI) studies with twin samples have shown moderate to high heritability in white matter microstructure. This study investigates the genetic and environmental contributions of another widely used diffusion MRI model not yet applied to twin studies, neurite orientation dispersion and density imaging (NODDI). The NODDI model is a multicompartment model of the diffusion-weighted MRI signal, providing estimates of neurite density (ND) and the orientation dispersion index (ODI). A cohort of monozygotic (MZ) and same-sex dizygotic (DZ) twins (N = 460 individuals) between 13 and 24 years of age were scanned with a multi-shell diffusion weighted imaging protocol. Select white matter (WM) regions of interest (ROI) were extracted. Biometric structural equation modeling estimated the relative contributions from additive genetic (A) and common (C) and unique environmental (E) factors. Genetic factors for the NODDI measures accounted for 91% and 65% of the variation of global ND and ODI, respectively, compared with 83% for FA. We observed higher heritability for ND than both FA and ODI in 25 of 30 discrete white matter regions that we examined, suggesting ND may be more sensitive to underlying genetic sources of variation. This study demonstrated that genetic factors play a key role in the development of white matter microstructure using both DTI and NODDI., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Clinical registry participation is a measure of healthcare quality. Limited knowledge exists on Australian hospitals' participation in clinical registries and whether this registry data informs quality improvement initiatives., Objective: To identify participation in clinical registries, determine if registry data inform quality improvement initiatives, and identify registry participation enablers and clinicians' educational needs to improve use of registry data to drive practice change., Methods: A self-administered survey was distributed to staff coordinating registries in seven hospitals in New South Wales, Australia. Eligible registries were international-, national- and state-based clinical, condition-/disease-specific and device/product registries., Results: Response rate was 70% (97/139). Sixty-two (64%) respondents contributed data to 46 eligible registries. Registry reports were most often received by nurses (61%) and infrequently by hospital executives (8.4%). Less than half used registry data 'always' or 'often' to influence practice improvement (48%) and care pathways (49%). Protected time for data collection (87%) and benchmarking (79%) were 'very likely' or 'likely' to promote continued participation. Over half 'strongly agreed' or 'agreed' that clinical practice improvement training (79%) and evidence-practice gap identification (77%) would optimize use of registry data., Conclusions: Registry data are generally only visible to local speciality units and not routinely used to inform quality improvement. Centralized on-going registry funding, accessible and transparent integrated information systems combined with data informed improvement science education could be first steps to promote quality data-driven clinical improvement initiatives., (© The Author(s) 2021. Published by Oxford University Press on behalf of International Society for Quality in Health Care. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Aedes albopictus is a competent vector of numerous pathogens, representing a range of transmission cycles involving unique hosts. Despite the important status of this vector, variation in its feeding patterns is poorly understood. We examined the feeding patterns of Ae. albopictus utilizing resting collections in Long Island, NY, and contextualized blood meal sources with host availability measured by household interviews and camera traps. We identified 90 blood meals, including 29 humans, 22 cats, 16 horses, 12 opossums, 5 dogs, 2 goats, and 1 each of rabbit, rat, squirrel, and raccoon. This is only the third study of Ae. albopictus blood feeding biology that quantitatively assessed domestic host availability and is the first to do so with wild animals. Host feeding indices showed that cats and dogs were fed upon disproportionately often compared with humans. Forage ratios suggested a tendency to feed on cats and opossums and to avoid raccoons, squirrels, and birds. This feeding pattern was different from another published study from Baltimore, where Ae. albopictus fed more often on rats than humans. To understand whether these differences were because of host availability or mosquito population variation, we compared the fitness of New York and Baltimore Ae. albopictus after feeding on rat and human blood. In addition, we examined fitness within the New York population after feeding on human, rat, cat, horse, and opossum blood. Together, our results do not indicate major mosquito fitness differences by blood hosts, suggesting that fitness benefits do not drive Northeastern Ae. albopictus feeding patterns.

Disturbances in positive affect and reductions in social reward/interpersonal pleasure are common across a range of clinical disorders and are often related. We examined the relationship between the Anticipatory and Consummatory Interpersonal Pleasure Scale (ACIPS-A), and other measures of positive affect in adolescents in a genetically informative research design. The sample consisted of 177 MZ and 136 same sex DZ twins drawn from a study of adolescent twins (M = 16.4 ± .97 years) who were part of the Wisconsin Twin Project. The self-report questionnaires included the Behavioral Activation Scale (BAS), Psychological Well-Being Scale, revised Early Adolescent Temperament Questionnaire (EATQR) and the adolescent version of the ACIPS (ACIPS-A). Structural equation modeling estimated the relative contribution of genetic and environmental factors to the phenotypic variance in each of the measures. Follow-up bivariate analyses parsed the genetic and environmental contributions to the phenotypic covariances between the ACIPS-A and each of the other measures of positive affect. We found evidence of moderate heritability for the ACIPS-A scale scores. Overall, models specifying additive genetic and unique environmental effects (AE models) were the most parsimonious models for each of the measures. Several of the measures showed moderate positive phenotypic intercorrelations, and all but one of these intercorrelations showed significant partial genetic underpinnings. Moreover, the bivariate biometric analyses indicated that the ACIPS-A also captures unique heritable variation. Thus, the ACIPS-A captures unique heritable contributions to social/interpersonal pleasure, as well as shared genetic variance with other measures of positive affectivity., Competing Interests: Conflict of interests: None.

Parental alcohol use disorder (AUD) is a substantiated risk factor for adolescent externalizing psychopathology; however, the level of specificity at which risk from parental AUD is transmitted to adolescent offspring should be interrogated further. The current study modeled competing factor structures of psychopathology in a sample of 502 adolescent twin pairs (M age  = 13.24 years) and tested associations with mother and father AUD. The bifactor model exhibited the best fit to the data when contrasted with correlated factors and general factor models. Paternal AUD predicted the externalizing and internalizing correlated factors, the adolescent P-factor but not the residual externalizing and internalizing factors, and the general factor. No significant associations with maternal AUD were noted. Lastly, the latent factors of adolescent psychopathology were all moderately heritable (h 2  = 0.44-0.59) and influenced by the nonshared environment. Shared genetic factors primarily explained externalizing and internalizing covariance. Findings suggest that efforts to mitigate risk in offspring of fathers exhibiting AUD require broader approaches that address the full range of adolescent symptomology., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objectives: The Pre-school Osteoarticular Infection (POI) study aimed to describe the burden of disease, epidemiology, microbiology and treatment of acute osteoarticular infections (OAI) and the role of Kingella kingae in these infections., Methods: Information about children 3-60 months of age who were hospitalized with an OAI to 11 different hospitals across Australia and New Zealand between January 2012 and December 2016 was collected retrospectively., Results: A total of 907 cases (73%) were included. Blood cultures grew a likely pathogen in only 18% (140/781). The peak age of presentation was 12 to 24 months (466/907, 51%) and Kingella kingae was the most frequently detected microorganism in this age group (60/466, 13%). In the majority of cases, no microorganism was detected (517/907, 57%). Addition of PCR to culture increased detection rates of K. kingae. However, PCR was performed infrequently (63/907, 7%)., Conclusions: This large multi-national study highlights the need for more widespread use of molecular diagnostic techniques for accurate microbiological diagnosis of OAI in pre-school aged children. The data from this study supports the hypothesis that a substantial proportion of pre-school aged children with OAI and no organism identified may in fact have undiagnosed K. kingae infection. Improved detection of Kingella cases is likely to reduce the average length of antimicrobial treatment., Competing Interests: Declaration of Competing Interest The study was endorsed by the Australasian Society for Infectious Diseases (ASID) Clinical Research Network and the pediatric subgroup (ANZPID) of ASID. The authors declare no competing interests., (Copyright © 2021. Published by Elsevier Ltd.)

Maternal and environmental factors influence brain networks and architecture via both physiological pathways and epigenetic modifications. In particular, prenatal maternal depression and anxiety symptoms appear to impact infant white matter (WM) microstructure, leading us to investigate whether epigenetic modifications (i.e., DNA methylation) contribute to these WM differences. To determine if infants of women with depression and anxiety symptoms exhibit epigenetic modifications linked to neurodevelopmental changes, 52 umbilical cord bloods (CBs) were profiled. We observed 219 differentially methylated genomic positions (DMPs; FDR p < 0.05) in CB that were associated with magnetic resonance imaging measures of WM microstructure at 1 month of age and in regions previously described to be related to maternal depression and anxiety symptoms. Genomic characterization of these associated DMPs revealed 143 unique genes with significant relationships to processes involved in neurodevelopment, GTPase activity, or the canonical Wnt signaling pathway. Separate regression models for female (n = 24) and male (n = 28) infants found 142 associated DMPs in females and 116 associated DMPs in males (nominal p value < 0.001, R > 0.5), which were annotated to 98 and 81 genes, respectively. Together, these findings suggest that umbilical CB DNA methylation levels at birth are associated with 1-month WM microstructure.

Adolescents experience profound neuroendocrine changes, including hormone "coupling" between cortisol, testosterone, and dehydroepiandrosterone. Emerging research has only begun to elucidate the role of hormone coupling, its genetic and environmental etiology, and the extent to which coupling is impacted by gender, puberty, and family context. We included measures on parent and child mental health, parenting stress, and family conflict of 444 twin pairs and their parents across two timepoints, when youth were on average 8 and 13 years old, respectively. Structural equation models examined the impact of family context effects on coupling during adolescence. Biometric twin models were then used to probe additive genetic, shared, and non-shared environmental effects on hormone coupling. Hormones were more tightly coupled for females than males, and coupling was sensitive to parental depression and co-twin psychopathology symptoms and stress exposure in females. The association between family context and coupling varied across specific neuroendocrine measures and was largely distinct from pubertal maturation. Biometric models revealed robust shared and non-shared environmental influences on coupling. We found that family antecedents modify the strength of coupling. Environmental influences account for much of the variation on coupling during puberty. Gender differences were found in genetic influences on coupling., (© 2020 Wiley Periodicals LLC.)

Clarifying longitudinal, behavioral predictors for adolescent suicidality could enhance prediction and treatment efforts. We examined whether childhood attentional focusing, persistence, and problem-solving behavior are associated with risk for adolescent suicidal ideation. Participants were 116 twins, 40 of whom endorsed active suicidal ideation (i.e., probands), probands' cotwins, and matched controls. Higher scores on a composite measure derived at mean age 7.7 years of (1) effort and work duration during two childhood problem-solving tasks (untangling yarn and attempting to solve an unsolvable puzzle), (2) mother reported attentional focusing, and (3) observer reported persistence predicted decreased risk for suicidal ideation at mean age 14.4 years. This prediction held when comparing probands with controls (B = -1.01, SE = 0.38, p = 0.01, OR = 0.37) and with their cotwins (B = -0.86, SE = 0.38, p = 0.02, OR = 0.42). Our findings indicate that childhood problem-solving behavior relates meaningfully to risk for suicidal thoughts approximately 7 years later, on average. These results underscore how longitudinal behavioral risk factors could enhance prediction and treatment of adolescent suicidal ideation.

In this study, we test the performance of a compact gas chromatograph with photoionization detector (GC-PID) and optimize the configuration to detect ambient (sub-ppb) levels of benzene, toluene, ethylbenzene, and xylene isomers (BTEX). The GC-PID system was designed to serve as a relatively inexpensive (~10 k USD) and field-deployable air toxic screening tool alternative to conventional benchtop GCs. The instrument uses ambient air as a carrier gas and consists of a Tenax-GR sorbent-based preconcentrator, a gas sample valve, two capillary columns, and a photoionization detector (PID) with a small footprint and low power requirement. The performance of the GC-PID has been evaluated in terms of system linearity and sensitivity in field conditions. The BTEX-GC system demonstrated the capacity to detect BTEX at levels as high as 500 ppb with a linear calibration range of 0-100 ppb. A detection limit lower than 1 ppb was found for all BTEX compounds with a sampling volume of 1 L. No significant drift in the instrument was observed. A time-varying calibration technique was established that requires minimal equipment for field operations and optimizes the sampling procedure for field measurements. With an analysis time of less than 15 min, the compact GC-PID is ideal for field deployment of background and polluted atmospheres for near-real time measurements of BTEX. The results highlight the application of the compact and easily deployable GC-PID for community monitoring and screening of air toxics.

Background: Sugar feeding is an important behavior which may determine vector potential of female mosquitoes. Sugar meals can reduce blood feeding frequency, enhance survival, and decrease fecundity, as well as provide energetic reserves to fuel energy intensive behaviors such as mating and host seeking. Sugar feeding behavior can be harnessed for vector control (e.g. attractive toxic sugar baits). Few studies have addressed sugar feeding of Aedes albopictus, a vector of arboviruses of public health importance, including dengue and Zika viruses. To address this knowledge gap, we assessed sugar feeding patterns of Ae. albopictus for the first time in its invasive northeastern USA range., Methodology/principal Findings: Using the cold anthrone fructose assay with robust sample sizes, we demonstrated that a large percentage of both male (49.6%) and female (41.8%) Ae. albopictus fed on plant or homopteran derived sugar sources within 24 hrs prior to capture. Our results suggest that sugar feeding behavior increases when environmental conditions are dry (high saturation deficit) and may vary by behavioral status (host seeking vs. resting). Furthermore, mosquitoes collected on properties with flowers (>3 blooms) had higher fructose concentrations compared to those collected from properties with few to no flowers (0-3)., Conclusions/significance: Our results provide the first evidence of Ae. albopictus sugar feeding behavior in the Northeastern US and reveal relatively high rates of sugar feeding. These results suggest the potential success for regional deployment of toxic sugar baits. In addition, we demonstrate the impact of several environmental and mosquito parameters (saturation deficit, presence of flowers, host seeking status, and sex) on sugar feeding. Placing sugar feeding behavior in the context of these environmental and mosquito parameters provides further insight into spatiotemporal dynamics of feeding behavior for Ae. albopictus, and in turn, provides information for evidence-based control decisions., Competing Interests: The authors have declared that no competing interests exist.

Early infancy is characterized by rapid brain development that occurs alongside, and in response to, the development of cognitive and behavioral functions, including attention. Infants' ability to orient and sustain attention to stimuli develops in concert with refinement of the orienting network in frontoparietal regions of the brain. Infants (n = 97) underwent magnetic resonance imaging at one-month of age and data were fit to a diffusion tensor imaging model to calculate fractional anisotropy (FA) and radial diffusivity (RD), as well as to a neurite orientation dispersion and density imaging model to calculate intracellular volume fraction (ν ic ). Infant attention was assessed at six months of age using a dynamic puppet task (Cuevas and Bell, 2014). Infants with higher FA in the corpus callosum and anterior cingulum showed increased orienting behaviors. Our findings indicate that increased microstructure of the white matter tracts in the orienting network may play a role in the early neurodevelopment of attentional orienting behaviors., (Published by Elsevier Ltd.)

Objective: Research suggests that higher childhood self-regulation (CSR) predicts lower adiposity in adolescence. However, it is unclear whether this relationship differs by sex or by baseline weight status. Thus, this study investigated these questions in a longitudinal, community-based cohort., Methods: The cohort included 221 girls and 214 boys. At age 9, CSR was assessed via parent/teacher reports of effortful control, and childhood BMI z scores (BMIz) were calculated from staff measurements. Late-adolescent waist-to-height ratio was based on staff measurements at age 18., Results: CSR has a small inverse correlation with concurrent childhood BMIz in girls, but not in boys. Prospectively, however, CSR has a small inverse association with late-adolescent weight-to-height ratio in both sexes, after adjusting for childhood BMIz and other childhood predictors. This prospective association is marginally stronger for girls with higher (vs. lower) childhood BMIz., Conclusions: CSR inversely predicts changes in adiposity across adolescence in both sexes, with some evidence that this association is stronger for girls with higher (vs. lower) childhood adiposity. However, this inverse association between CSR and adiposity may emerge earlier in girls. Future research should examine the causal status of CSR and its relationship to behaviors (e.g., diet)., (© 2020 The Obesity Society.)

Profiles of infant temperament were derived from 990 infants at 6 and 12 months of age using observed measures from the Laboratory Temperament Assessment Battery. Mothers and fathers completed questionnaires measuring parent affect and stress. Four profiles emerged at each age (typical, low negative, withdrawn/inhibited, and positive/active or low reactive) using latent profile analysis. Temperament profiles show some evidence of stability and heritability, particularly for the withdrawn/inhibited group. In addition, profiles relate to parent affect and stress in different ways for mothers and fathers. Results highlight the utility of a person-centered approach to temperamental research and are discussed in relation to developmental patterns of infant temperament., (© 2019 Society for Research in Child Development.)

Symptoms of attention-deficit/hyperactivity disorder (ADHD) and anxiety are common during adolescence and frequently co-occur. However, the genetic and environmental influences that underlie this co-occurrence are understudied. Using a large twin sample (N = 1,017), we examined cross-sectional genetic and environmental influences on ADHD and anxiety symptoms during childhood. We also explored whether these influences were shared with attentional control, a putative mechanism for symptom comorbidity. We found evidence for common genetic and nonshared environmental influences on the covariation among attentional control, ADHD, and anxiety symptoms, supporting the putative role of attentional control as a mechanism by which comorbid problems may develop. Genetic factors also accounted for symptom co-occurrence after controlling for covariation with attentional control, suggesting the presence of additional unmeasured mechanisms., (© 2019 Society for Research on Adolescence.)

The Wisconsin Twin Project encompasses nearly 30 years of longitudinal research that spans infancy to early adulthood. The twin sample was recruited from statewide birth records for birth cohorts 1989-2004. We summarize early recruitment, assessment, retention and recently completed twin neuroimaging studies. In addition to the focal twins, longitudinal data were also collected from two parents and nontwin siblings. Our adolescent and young adult neuroimaging sample (N = 600) completed several previous behavioral and environmental assessments, beginning shortly after birth. The extensive phenotyping is meant to support a range of empirical investigations with potentially differing theoretical perspectives.

Purpose: NODDI is widely used in parameterizing microstructural brain properties. The model includes three signal compartments: intracellular, extracellular, and free water. The neurite compartment intrinsic parallel diffusivity (d∥) is set to 1.7 μm2⋅ms-1, though the effects of this assumption have not been extensively explored. This work investigates the optimality of d∥ = 1.7 μm2⋅ms-1 under varying imaging protocol, age groups, sex, and tissue type in comparison to other biologically plausible values of d∥., Methods: Model residuals were used as the optimality criterion. The model residuals were evaluated in function of d∥ over the range from 0.5 to 3.0 μm2⋅ms-1. This was done with respect to tissue type (i.e., white matter versus gray matter), sex, age (infancy to late adulthood), and diffusion-weighting protocol (maximum b-value). Variation in the estimated parameters with respect to d∥ was also explored., Results: Results show d∥ = 1.7 μm2⋅ms-1 is appropriate for adult brain white matter but it is suboptimal for gray matter with optimal values being significantly lower. d∥ = 1.7 μm2⋅ms-1 was also suboptimal in the infant brain for both white and gray matter with optimal values being significantly lower. Minor optimum d∥ differences were observed versus diffusion protocol. No significant sex effects were observed. Additionally, changes in d∥ resulted in significant changes to the estimated NODDI parameters., Conclusion: The default (d∥) of 1.7 μm2⋅ms-1 is suboptimal in gray matter and infant brains., Competing Interests: The authors have declared that no competing interests exist.

De novo pathogenic variants in the human immunodeficiency virus enhancer type I binding protein 2 (HIVEP2) gene, a large transcription factor predominantly expressed in the brain have previously been associated with intellectual disability (ID) and dysmorphic features in nine patients. We describe the phenotype and genotype of two additional patients with novel de novo pathogenic HIVEP2 variants, who have previously unreported features, including hyperphagia and Angelman-like features. Exome sequencing was utilized in the investigation of the patients who had previously incurred a rigorous genetic workup for their neurodevelopmental delay, and in whom no genetic cause had been detected. Information pertaining to phenotype and genotype for new patients was collated along with data from previous reports, showing that the phenotypic spectrum of patients with HIVEP2 variants is broader than first noted. Additional characteristics are: an increased body mass index; and features of Angelman-like syndromes including: ID, limited speech, post-natal microcephaly, and hypotonia. Dysmorphic features vary between patients. As yet, no clear association between the type of gene aberration and phenotype can be concluded. HIVEP2-related ID needs to be considered in the differential diagnosis of patients with Angelman-like phenotypes and hyperphagia, and whole-exome sequencing should be considered in the genetic diagnostic armamentarium for patients with ID of inconclusive etiology., (© 2019 Wiley Periodicals, Inc.)

The Wisconsin Twin Project comprises multiple longitudinal studies that span infancy to early adulthood. We summarize recent papers that show how twin designs with deep phenotyping, including biological measures, can inform questions about phenotypic structure, etiology, comorbidity, heterogeneity, and gene-environment interplay of temperamental constructs and mental and physical health conditions of children and adolescents. The general framework for investigations begins with rich characterization of early temperament and follows with study of experiences and exposures across childhood and adolescence. Many studies incorporate neuroimaging and hormone assays.

Background: The AspireAssist is the first Food and Drug Administration-approved endoluminal device indicated for treatment of class II and III obesity., Objectives: We earlier reported 1-year results of the PATHWAY study. Here, we report 4-year outcomes., Setting: United States-based, 10-center, randomized controlled trial involving 171 participants with the treatment arm receiving Aspiration Therapy (AT) plus Lifestyle Therapy and the control arm receiving Lifestyle Therapy (2:1 randomization)., Methods: AT participants were permitted to continue in the study for an additional year up to a maximum of 5 years providing they maintained at least 10% total weight loss (TWL) from baseline at each year end. For AT participants who continued the study, 5 medical monitoring visits were provided at weeks 60, 68, 76, 90, and 104 and thereafter once every 13 weeks up to week 260. Exclusion criteria were a history of eating disorder or evidence of eating disorder on a validated questionnaire. Follow-up weight, quality of life, and co-morbidities were compared with the baseline levels. In addition, rates of serious adverse event, persistent fistula, withdrawal, and A-tube replacement were reported. All analyses were performed using a per-protocol analysis., Results: Of the 82 AT participants who completed 1 year, 58 continued to this phase of the trial. Mean baseline body mass index of these 58 patients was 41.6 ± 4.5 kg/m 2 . At the end of first year (at the beginning of the follow-up study), these 58 patients had a body mass index of 34.1 ± 5.4 kg/m 2 and had achieved an 18.3 ± 8.0% TWL. On a per protocol basis, patients experienced 14.2%, 15.3%, 16.6%, and 18.7% TWL at 1, 2, 3, and 4 years, respectively (P < .01 for all). Forty of 58 patients (69%) achieved at least 10% TWL at 4 years or at time of study withdrawal. Improvements in quality of life scores and select cardiometabolic parameters were also maintained through 4 years. There were 2 serious adverse events reported in the second through fourth years, both of which resolved with removal or replacement of the A tube. Two persistent fistulas required surgical repair, representing approximately 2% of all tube removals. There were no clinically significant metabolic or electrolytes disorders observed, nor any evidence for development of any eating disorders., Conclusions: The results of this midterm study have shown that AT is a safe, effective, and durable weight loss alternative for people with class II and III obesity and who are willing to commit to using the therapy and adhere to adjustments in eating behavior., (Copyright © 2019. Published by Elsevier Inc.)

The parent-child relationship impacts many later social and cognitive outcomes. The current study compared correlates of mother versus father dyadic interactions with their twin children in 503 families at 36 months of age. Measures included parent reported child temperament, observed parents' marital quality and affect, and parents' sensitivity, responsivity, and growth fostering with their children. Different patterns emerged for mothers and fathers: marital quality related to higher sensitivity for fathers, whereas positivity related to higher sensitivity for mothers. Child inhibitory control was related to fathers' response to child distress and mothers' use of cognitive growth fostering. In sum, parental engagement varied depending on marital and child factors, although different patterns emerged for mothers and fathers. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Peer victimization impacts 13% of adolescents worldwide (Currie et al. 2012). Despite its prevalence and associated adverse outcomes, global cognitive processes that could be affected by peer victimization have not been thoroughly investigated. Using a monozygotic (MZ) twin difference design that rigorously controls for the influence of genetic and familial level confounders, we examined the relation between peer victimization exposure and selective attention processes during an affective go/no go task. Twins who experienced more severe peer victimization were biased towards detecting goal relevant stimuli during the task. Our findings suggest an environmentally salient relation between peer victimization and goal oriented selective attention. Future work should investigate how this process might serve to enhance or buffer risk of peer victimization exposure for developing later adverse outcomes.

Objective: Sensory overresponsivity (SOR) is characterized by challenges in integrating and responding to everyday sensory experiences. Obsessive-compulsive disorder (OCD) is characterized by intrusive thoughts, ritualistic behaviors, and sensory phenomena. There is some evidence that individuals with co-occurring symptoms of SOR and OCD experience more severe anxiety than those with symptoms of OCD alone, but most studies employed small numbers of participants (typically with an OCD diagnosis) assessed at a single time point. Our 2-fold objective was to replicate previous research showing an association between OCD symptoms and SOR symptoms concurrently and to extend these analyses longitudinally in a large, birth-register-based sample., Method: Twins (N = 1613) and their primary caregivers participated in a multimodal, multimethod, longitudinal study. Primary caregivers completed the SOR inventory for their offspring at the age of 8 years, and twins completed the adult sensory profile at the age of 13 years. Parents completed the OCD module of the Diagnostic Interview Schedule for Children-IV when twins were 8 years; twins completed the same module at 13 years. Linear regression models tested for the concurrent and longitudinal associations between SOR and OCD controlling for socioeconomic status., Results: Concurrently, participants' likelihood of exhibiting OCD symptoms increased with each symptom of tactile or auditory overresponsivity at 8 years and 13 years (odds ratio = 1.1-2.7). However, SOR measured at age 8 years was unrelated to adolescent OCD symptoms at 13 years and vice versa., Conclusion: SOR symptoms, although significantly related to concurrent OCD symptoms, do not appear to precede OCD symptoms, suggesting that SOR symptoms may reflect another type of OCD sensory phenomenon rather than a comorbid condition.

Although suicide remains a leading cause of death for adolescents, risk factors beyond diagnoses and suicide attempt history remain unclear. We examined whether cognitive style and temperament impact risk for an early, yet still clinically relevant and distressing, form of suicidality: active suicidal ideation. We used binary logistic regression to test whether brooding, inattention, and impulsivity predicted significantly increased risk for suicidal ideation in a sample of 134 twins, 46 of whom endorsed active suicidal ideation (i.e., probands), as well as probands' cotwins and matched controls. When comparing probands with controls and controlling for depression diagnoses, brooding (B = 0.73, Odds Ratio [OR] = 2.07, p = 0.021), inattention (B = 1.09, OR = 2.98, p < 0.001), and impulsivity (B = 0.91, OR = 2.47, p = 0.001) differentiated probands from controls, individually. We compared probands with their cotwins using the same approach, which allowed us to account for variance in suicidal ideation risk related to twins' shared, familial characteristics (e.g., prenatal environment, neighborhood); inattention was the only significant predictor of suicidal ideation risk (B = 0.66, OR = 1.93, p = 0.020). We then fit a logistic regression model that included all three predictors. Only inattention predicted significantly increased likelihood of suicidal ideation in proband versus controls and proband versus cotwin comparisons (B = 0.88, OR = 2.40, p = 0.024 and B = 0.67, OR = 1.96, p = 0.045, respectively). These results highlight the potential utility of examining novel, more proximal risk factors for suicidal ideation in addition to more established distal factors, like suicide attempt history and psychiatric diagnoses.

Importance: Maternal depression and anxiety can have deleterious and lifelong consequences on child development. However, many aspects of the association of early brain development with maternal symptoms remain unclear. Understanding the timing of potential neurobiological alterations holds inherent value for the development and evaluation of future therapies and interventions., Objective: To examine the association between exposure to prenatal maternal depression and anxiety symptoms and offspring white matter microstructure at 1 month of age., Design, Setting, and Participants: This cohort study of 101 mother-infant dyads used a composite of depression and anxiety symptoms measured in mothers during the third trimester of pregnancy and measures of white matter microstructure characterized in the mothers' 1-month offspring using diffusion tensor imaging and neurite orientation dispersion and density imaging performed from October 1, 2014, to November 30, 2016. Magnetic resonance imaging was performed at an academic research facility during natural, nonsedated sleep., Main Outcomes and Measures: Brain mapping algorithms and statistical models were used to evaluate the association between maternal depression and anxiety and 1-month infant white matter microstructure as measured by diffusion tensor imaging and neurite orientation dispersion and density imaging findings., Results: In the 101 mother-infant dyads (mean [SD] age of mothers, 33.22 [3.99] years; mean age of infants at magnetic resonance imaging, 33.07 days [range, 18-50 days]; 92 white mothers [91.1%]; 53 male infants [52.5%]), lower 1-month white matter microstructure (decreased neurite density and increased mean, radial, and axial diffusivity) was associated in right frontal white matter microstructure with higher prenatal maternal symptoms of depression and anxiety. Significant sex × symptom interactions with measures of white matter microstructure were also observed, suggesting that white matter development may be differentially sensitive to maternal depression and anxiety symptoms in males and females during the prenatal period., Conclusions and Relevance: These data highlight the importance of the prenatal period to early brain development and suggest that the underlying white matter microstructure is associated with the continuum of prenatal maternal depression and anxiety symptoms.

When a brain network is constructed by an existing parcellation method, the topological structure of the network changes depending on the scale of the parcellation. To avoid the scale dependency, we propose to construct a nested hierarchical structural brain network by subdividing the existing parcellation hierarchically. The method is applied in diffusion tensor imaging study of 111 twins in characterizing the topology of the brain network. The genetic contribution of the whole brain structural connectivity is determined and shown to be robustly present over different network scales.

The authors regret that, in this article, there was an error in the analyses comparing infant male and female regional brain volume differences.

The developing brain undergoes systematic changes that occur at successive stages of maturation. Deviations from the typical neurodevelopmental trajectory are hypothesized to underlie many early childhood disorders; thus, characterizing the earliest patterns of normative brain development is essential. Recent neuroimaging research provides insight into brain structure during late childhood and adolescence; however, few studies have examined the infant brain, particularly in infants under 3 months of age. Using high-resolution structural MRI, we measured subcortical gray and white matter brain volumes in a cohort (N = 143) of 1-month infants and examined characteristics of these volumetric measures throughout this early period of neurodevelopment. We show that brain volumes undergo age-related changes during the first month of life, with the corresponding patterns of regional asymmetry and sexual dimorphism. Specifically, males have larger total brain volume and volumes differ by sex in regionally specific brain regions, after correcting for total brain volume. Consistent with findings from studies of later childhood and adolescence, subcortical regions appear more rightward asymmetric. Neither sex differences nor regional asymmetries changed with gestation-corrected age. Our results complement a growing body of work investigating the earliest neurobiological changes associated with development and suggest that asymmetry and sexual dimorphism are present at birth.

Reactions to sensory experiences are an overlooked correlate of affective regulation, despite the importance of bodily states on psychological processes. Children who display sensory over-responsivity (i.e., adverse reactions to typical sensations) are at greater risk for developing affective disorders. We extended this literature to adolescents and their middle-aged parents. Participants in a birth record-based study of families of adolescent twins (N = 506 families; 1012 adolescents; 53% female) completed a subset of items from the Adult Sensory Profile. We derived adolescent self-reported internalizing disorder symptoms and parent affective diagnoses from structured diagnostic interviews. Structural equation models tested the relationship between parent sensory over-responsivity symptoms and affective diagnoses and their adolescent offspring's sensory over-responsivity and internalizing symptoms. Adolescent sensory over-responsivity symptoms were correlated with internalizing disorder symptoms. Parents with a diagnosis of anxiety or depression (mothers only) reported more frequent SOR symptoms than parents without a diagnosis. Parent depression was significantly related to adolescent sensory over-responsivity symptoms, over and above parent sensory over-responsivity symptoms (β = 0.26, p < 0.001 for mothers; β = 0.13, p = 0.004 for fathers). Father alcohol abuse/dependency also predicted offspring sensory over-responsivity symptoms. Offspring of parents with affective disorders were at additional risk for sensory dysregulation via parents' influence on offspring internalizing problems.

Aims and Objectives: To explore the pain management experiences of recently discharged adult trauma patients and the discharge practices of the treating hospital., Background: Adult trauma patients are not always able to manage their pain effectively and as a result often experience intense and enduring injury pain at home. They describe their pain experience as unique and debilitating, and report feeling uninformed at hospital discharge. There is a need to understand what is fundamentally required for this population at hospital discharge, to facilitate competent pain management and promote best possible outcomes., Design: A mixed methods convergent study design., Methods: The quantitative results (incidence, intensity and impact of injury pain and the barriers to effective pain management) were merged with the qualitative results (patient experiences and beliefs) to produce greater understanding about the reasons behind the pain management practices of participants., Results: Integration of the quantitative and qualitative data produced four new themes. These themes demonstrate that recently discharged adult trauma patients do not have the knowledge or experience to understand or manage their injury pain effectively at home. Inadequate information and education by clinicians, at hospital discharge, contribute to this insufficiency., Conclusions: Clinicians need to understand the trauma patient pain experience to appreciate the importance of their discharge practices. Increased understanding and implementation of evidence-informed discharge processes would improve current discharge practices and ultimately support and improve the trauma patient's injury pain management practices at home., Relevance to Clinical Practice: By understanding the patient perspective in the pain management of injuries, clinicians are better able to appreciate what hospital discharge practices and information are genuinely required by the trauma patient to manage their pain effectively at home, potentially preventing the long-term consequences of injury pain., (© 2017 John Wiley & Sons Ltd.)

Introduction: Pain following injury is often intense, prolonged and debilitating. If poorly managed, this acute pain has the potential to delay rehabilitation and lead to chronic pain. Recent quantitative Australian research recommends implementing further information and interventions to improve trauma patient outcomes, however, to ensure effectiveness, exploration of the patient perspective is imperative to ensure the success of future pain management strategies. This study aimed to gain understanding about the experience of pain management using prescribed analgesic regimens of recently discharged adult trauma patients., Method: Semi-structured interviews were used to explore the experiences and understandings of trauma patients in managing pain using prescribed analgesic regimens during the initial post-hospital discharge period. Twelve participants were purposively selected over a 6-month period at a level one trauma outpatient clinic based on questionnaire responses indicating pain related concerns. Qualitative data were thematically analysed., Results: The overarching finding was that injuries and inadequate pain management incapacitate the patient at home. Four main themes were developed: injury pain is unique and debilitating; patients are uninformed at hospital discharge; patients have low confidence with pain management at home; and patients make independent decisions about pain management. Patients felt they were not given adequate information at hospital discharge to support them to make effective decisions about their pain management practices at home., Conclusion: There is a need for more inclusive and improved hospital discharge processes that includes patient and family education around pain management following injury. To achieve this, clinician education, support and training is essential., (Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.)

The etiology of individual differences in human anxiousness is complex and includes contributions from genetic, epigenetic (i.e., DNA methylation) and environmental factors. Past genomic approaches have been limited in their ability to detect human anxiety-related differences in these factors. To overcome these limitations, we employed both a multi-dimensional characterization method, to select monozygotic twin pairs discordant for anxiety, and whole genome DNA methylation sequencing. This approach revealed 230 anxiety-related differentially methylated loci that were annotated to 183 genes, including several known stress-related genes such as NAV1, IGF2, GNAS, and CRTC1. As an initial validation of these findings, we tested the significance of an overlap of these data with anxiety-related differentially methylated loci that we previously reported from a key neural circuit of anxiety (i.e., the central nucleus of the amygdala) in young monkeys and found a significant overlap (P-value < 0.05) of anxiety-related differentially methylated genes, including GNAS, SYN3, and JAG2. Finally, sequence motif predictions of all the human differentially methylated regions indicated an enrichment of five transcription factor binding motifs, suggesting that DNA methylation may regulate gene expression by mediating transcription factor binding of these transcripts. Together, these data demonstrate environmentally sensitive factors that may underlie the development of human anxiety.

Aims and Objectives: To identify barriers to adherence with prescribed analgesic regimens in recently discharged trauma patients., Background: Trauma pain severely interferes with the life of healthy and often working individuals with intense and enduring pain experienced at home following discharge. The reasons for this are unclear considering discharge information (including discharge referral letters and nursing discharge checklists) and analgesics (scripts and/or medication) are routinely provided to patients at hospital discharge., Design: A prospective exploratory study., Methods: Between July-December 2014, 82 recently discharged adult trauma patients completed a questionnaire about their injury-related pain and pain management experiences posthospital discharge from a level one trauma centre. For 77 of these participants, medical records were reviewed for documentation regarding pain, analgesic consumption and hospital discharge processes., Results: Sixty-five participants (84%) consumed opioids prior to discharge, with two-thirds (65%) of these participants given a script for and/or opioid medication at hospital discharge. Of the 77 participants who took analgesics following discharge, 26 (34%) indicated they had experienced side effects and 16 (21%) used pain medication not prescribed by a doctor. Whilst it was documented that discharge letters were given to 25 participants (32%) at discharge and 13 participants (17%) had completed nursing discharge checklists, these participants reported the lowest pain severity and interference scores postdischarge., Conclusions: Insufficient information and analgesics given to trauma patients at hospital discharge and inconsistent and incomplete discharge processes fail to equip trauma patients to effectively manage their pain at home., Relevance to Clinical Practice: It is crucial that nurses and other healthcare professionals are aware of and actively contribute to correct and complete discharge processes. Effective patient and hospital facilitators can contribute to good pain management practices amongst recently discharged trauma patients, which will thereby improve the functional outcomes of this patient population., (© 2017 John Wiley & Sons Ltd.)

White matter microstructure, essential for efficient and coordinated transmission of neural communications, undergoes pronounced development during the first years of life, while deviations to this neurodevelopmental trajectory likely result in alterations of brain connectivity relevant to behavior. Hence, systematic evaluation of white matter microstructure in the normative brain is critical for a neuroscientific approach to both typical and atypical early behavioral development. However, few studies have examined the infant brain in detail, particularly in infants under 3 months of age. Here, we utilize quantitative techniques of diffusion tensor imaging and neurite orientation dispersion and density imaging to investigate neonatal white matter microstructure in 104 infants. An optimized multiple b-value diffusion protocol was developed to allow for successful acquisition during non-sedated sleep. Associations between white matter microstructure measures and gestation corrected age, regional asymmetries, infant sex, as well as newborn growth measures were assessed. Results highlight changes of white matter microstructure during the earliest periods of development and demonstrate differential timing of developing regions and regional asymmetries. Our results contribute to a growing body of research investigating the neurobiological changes associated with neurodevelopment and suggest that characteristics of white matter microstructure are already underway in the weeks immediately following birth.

Anxiety is linked to deficits in structural and functional connectivity between limbic structures and pre-frontal cortices. We employed a monozygotic (MZ) twin difference design to examine the relationship between structural characteristics of the uncinate fasciculus (UF) measured by Diffusion Tensor Imaging (DTI) and anxiety symptoms in a sample of N = 100 monozygotic (genetically identical), adolescent twins. The MZ difference design allowed us focus on environmental factors that vary within twin pairs while controlling for genetic and environmental factors shared by twin pairs. Twins aged 13-18 years reported on symptoms of generalized anxiety and social phobia prior to participating in a neuroimaging visit. Regions of interest from the JHU ICBM atlas, including uncinate fasciculus and sagittal stratum as a control tract, were registered to the study template. We incorporated multiple diffusion tensor measures to characterize the white matter differences. Within twin pairs, the more anxious twin exhibited decreased fractional anisotropy (t = -2.22, p = 0.032) and axial diffusivity (t = -2.38, p = 0.022) in the left UF compared to the less anxious twin, controlling for age and gender. This study demonstrated the feasibility and advantages of adopting the MZ twin design for DTI measures in neuroimaging research.

Asymmetry in cortical activity was tested for short- and long-term stability during the first year of life. Infants (N = 129) completed a total of four laboratory visits: two visits occurred about 1 week apart when infants were 6 months old, and two visits occurred about 1 week apart when infants were 12 months of age. At each laboratory visit, EEG readings were taken during five 1-min, neutral baselines as well as during a negative and a positive emotion-eliciting task. The stability of hemispheric asymmetry was assessed at midfrontal (F3/4, F7/8) and parietal (P3/4) electrode sites. Asymmetry in baseline and fear-eliciting episodes showed moderate short-term stability. Long-term stability was apparent when assessments were composited at 6 months and 12 months. Frontal asymmetry was greater than parietal asymmetry for baseline recordings. There was minimal evidence for stability in asymmetry during positive emotion tasks. Results are discussed with regard to the collection and interpretation of alpha asymmetry measures during infancy., (© 2017 Society for Psychophysiological Research.)

Two recent papers associated candidate genes with brooding rumination, a possible cognitive endophenotype for depression, in children ages 8-14 years. Stone et al. reported that BDNF val66met polymorphism predicted brooding in adolescence. Woody et al. reported that children carrying at least one copy of a CRHR1 TAT haplotype reported less brooding than their peers in the presence of maternal depression. We attempted to replicate and extend these findings in a sample of twins aged 12-16 years. We analyzed the BDNF val66met (rs6265) polymorphism and two (rs242924 and rs7209436) out of three single nucleotide polymorphisms (SNPs) that Woody et al. used to create a CRHR1 haplotype. We controlled for maternal history of depression and clustering within families. Unlike Stone et al., we found higher brooding among BDNF Met carriers. This main effect was qualified by an interaction with pubertal status, with the effect driven by more physically mature participants. Similar to Woody et al., we found an interaction between CRHR1 SNPs and maternal depression, with the homozygous minor genotype acting as a protective factor against brooding in the presence of maternal depression. Findings provide partial support for the influence of candidate genes in two environmentally sensitive systems on brooding.

Although a robust literature has linked stable, high levels of fear across childhood to increased risk for anxiety problems, less is known about alternative pathways to anxiety. We tested two putatively normative developmental pathways of early fearfulness for their distinct associations with behavioral (anxiety-related behaviors and symptoms) and biological (diurnal cortisol) markers of anxiety risk in middle childhood in a community-based sample (n = 107). Steeper increases in fear from 6 to 36 months predicted more parent-reported anxiety symptoms at age 8 years. In addition, children who exhibited steep increases in fear during infancy were overrepresented among children with diagnoses of separation anxiety disorder at age 8 years. Finally, we showed that steeper increases in fearfulness in infancy predicted flatter slopes of diurnal cortisol at age 8 years for girls. Thus, differences in stranger fear across infancy may indicate varying degrees of risk for anxious behaviors in later childhood.

We describe large-sample research using the Infant Laboratory Temperament Assessment Battery (Lab-TAB; Goldsmith and Rothbart, 1996) in 1,076 infants at 6 and 12 months of age. The Lab-TAB was designed to assess temperament dimensions through a series of episodes that mimic everyday situations. Our goal is to provide guidelines for scoring Lab-TAB episodes to derive temperament composites. We also present a set of analyses examining mean differences and stability of temperament in early infancy, gender differences in infant temperament, as well as a validation of Lab-TAB episodes and composites with parent reported Infant Behavior Questionnaire (IBQ; Rothbart, 1981) scales. In general, laboratory observed temperament was only modestly related to parent reported temperament. However, temperament measures were significantly stable across time and several gender differences that align with previous research emerged. In sum, the Lab-TAB usefully assesses individual differences in infant emotionality.

This study elucidates genetic influences on reflexive (as opposed to sustained) attention in children (aged 9-16 years; N = 332) who previously participated as infants in visual attention studies using orienting to a moving bar (Dannemiller, 2004). We investigated genetic associations with reflexive attention measures in infancy and childhood in the same group of children. The genetic markers (single nucleotide polymorphisms and variable number tandem repeats on the genes APOE, BDNF, CHRNA4, COMT, DRD4, HTR4, IGF2, MAOA, SLC5A7, SLC6A3, and SNAP25) are related to brain development and/or to the availability of neurotransmitters such as acetylcholine, dopamine, or serotonin. This study shows that typically developing children have differences in reflexive attention associated with their genes, as we found in adults (Lundwall, Guo & Dannemiller, 2012). This effort to extend our previous findings to outcomes in infancy and childhood was necessary because genetic influence may differ over the course of development. Although two of the genes that were tested in our adult study (Lundwall et al., 2012) were significant in either our infant study (SLC6A3) or child study (DRD4), the specific markers tested differed. Performance on the infant task was associated with SLC6A3. In addition, several genetic associations with an analogous child task occurred with markers on CHRNA4, COMT, and DRD4. Interestingly, the child version of the task involved an interaction such that which genotype group performed poorer on the child task depended on whether we were examining the higher or lower infant scoring group. These findings are discussed in terms of genetic influences on reflexive attention in infancy and childhood., (© 2015 John Wiley & Sons Ltd.)