An Integrated Approach to Address Perinatal Mental Health Within an Obstetrics Practice.

Outpatient perinatal care providers (one certified nurse-midwife, one nurse practitioner, and one physician assistant) at a high-volume, suburban health system in southeastern Pennsylvania developed and implemented a care model to identify and care for patients at risk for perinatal and postpartum mental health conditions. The program, Women Adjusting to Various Emotional States (WAVES), was created to bring the most up-to-date, evidence-based treatment recommendations to patients while addressing the increased demand placed on the health care system by pregnant and postpartum patients in need of psychiatric services. WAVES is a specialized program offered for anyone who is pregnant or up to one year postpartum who is struggling with mental health symptoms or concerns. Perinatal mood and anxiety disorders have become one of the most prevalent pregnancy ailments, yet mental health is not always addressed during routine prenatal care visits. Common obstacles to patients obtaining mental health care during pregnancy include lack of access, clinician gaps in knowledge, and stigma surrounding diagnoses. WAVES offers a method to empower perinatal providers with the education and tools to address this need. The model outlines how to appropriately assess, diagnose, manage, or refer patients for mental health services. Patient feedback has been overwhelmingly positive, and this novel care model shows great promise for the future of perinatal care. The development of integrated programs like WAVES may be a valuable resource to help combat the perinatal mental health epidemic.

Developmental associations between motor and communication outcomes in Fragile X syndrome: Variation in the context of co-occurring autism.

LAY ABSTRACT: Fragile X syndrome (FXS), the leading heritable cause of intellectual disability, has a co-occurrence rate of autism spectrum disorder (ASD) estimated at ~60%. Children with FXS experience delayed achievement and slower development of key motor abilities, which happens to an even greater extent for children with both FXS and ASD. A multitude of studies have demonstrated that motor abilities are foundational skills related to later communication outcomes in neurotypical development, as well as in the context of ASD. However, these associations remain unexamined in FXS, or FXS + ASD. In this study, we aimed to determine the associations between early motor skills and their rate of development on communication outcomes in FXS. Furthermore, we investigated whether these associations varied in the context of co-occurring FXS + ASD. Results revealed within-FXS variation in the context of co-occurring ASD between some aspects of motor development and communication outcomes, yet within-FXS consistency between others. Findings provide evidence for variability in developmental processes and outcomes in FXS in the context of co-occurring ASD and offer implications for intervention.

A holistic approach to fragile X syndrome integrated guidance for person-centred care.

BACKGROUND: The Fragile X community has expressed a desire for centralised, national guidelines in the form of integrated guidance for Fragile X Syndrome (FXS). METHODS: This article draws on existing literature reviews, primary research and clinical trials on FXS, a Fragile X Society conference workshop and first-hand experience of clinicians who have worked with those living with FXS over many years. RESULTS: The article scopes proposed integrated guidance over the life course, including appendices of symptoms, comorbidities and referral options for FXS and Fragile X Premutation Associated Conditions. CONCLUSION: Integrated guidance would provide an authoritative source for doctors, health professionals, therapists, care workers, social workers, educators, employers, families and those living with FXS, so that a holistic, person-centred approach can be taken across the United Kingdom to garner the best outcomes for those with FXS.

Association between goal nutrition and intubation in patients with bronchiolitis on noninvasive ventilation: A retrospective cohort study.

BACKGROUND: Acute bronchiolitis causes many hospitalizations in children younger than 2 years. Early enteral nutrition is associated with improved outcomes in these patients. However, often nutrition is withheld when patients require noninvasive respiratory support because of the risk of aspiration worsening respiratory failure, possibly requiring intubation. We hypothesize that achieving goal energy intake is associated with a lower intubation rate in hospitalized children with bronchiolitis who require noninvasive ventilation. METHODS: This retrospective cohort study examined the association between goal enteral nutrition (60% of dietary reference energy intake) and intubation rates. We grouped patients by severity of illness and compared intubation rates in those who met goal energy to those who did not. We use stratified analysis methods (for both level of respiratory support and feeding route) to evaluate progression to intubation. RESULTS: Of the 272 patients, 215 met goal feeds. These groups had similar demographics, but the goal-feeds group started on higher respiratory support in the pediatric intensive care unit. We found that 4.65% of the patients who met goal feeds required intubation compared with 24.6% of patients who did not meet goal feeds (P < 0.0001), even after controlling for respiratory status at admission and time of feed initiation and feeding route. CONCLUSION: We observed when adjusting for severity, feeding route, and respiratory support, achieving goal energy intake remained associated with a lower rate of intubation, without higher rates of aspiration. Confounding factors include practice variation and difference in severity of illness that objective scoring may have missed.

Behavioural and physiological indicators of anxiety reflect shared and distinct profiles across individuals with neurogenetic syndromes.

Anxiety is heightened in individuals with intellectual disability, particularly in those with specific neurogenetic syndromes. Assessment of anxiety for these individuals is hampered by a lack of appropriate measures that cater for communication impairment, differences in presentation, and overlapping features with co-occurring conditions. Here, we adopt a multi-method approach to identify fine-grained behavioural and physiological (via salivary cortisol) responses to anxiety presses in people with fragile X (FXS; n = 27; Mage = 20.11 years; range 6.32 - 47.04 years) and Cornelia de Lange syndromes (CdLS; n = 27; Mage = 18.42 years; range 4.28 - 41.08 years), two neurogenetic groups at high risk for anxiety, compared to neurotypical children (NT; n = 21; Mage = 5.97 years; range 4.34 - 7.30 years). Results indicate that physical avoidance of feared stimuli and proximity seeking to a familiar adult are prominent behavioural indicators of anxiety/stress in FXS and CdLS. Heightened pervasive physiological arousal was identified in these groups via salivary cortisol. An association between autistic characteristics and anxiety was evident in the FXS group but not in the CdLS group pointing to syndrome-specific nuances in the association between anxiety and autism. This study furthers understanding of the behavioural and physiological presentation of anxiety in individuals with intellectual disability and progresses theoretical developments regarding the development and maintenance of anxiety at the intersection of autism.

General practice experiences for parents of children with intellectual disability: a systematic review.

BACKGROUND: Parents of children diagnosed with intellectual disability are at increased risk of mental and physical health difficulties compared with other parents. They are likely to regularly seek medical treatment for their health concerns from general practice as well as on behalf of their child with intellectual disability, yet there is limited evaluation of the role general practice plays for this patient group. AIM: To explore parents' experiences of general practice support when caring for a child with intellectual disability. DESIGN & SETTING: Systematic review of studies reporting experiences of general practice as described by parents who care for children with intellectual disability. METHOD: Databases were searched using a pre-defined search strategy. Studies were included based on detailed inclusion criteria, title, abstract, and full-text screening. Quality assessment was conducted using the Mixed Methods Appraisal Tool (MMAT). A narrative synthesis was conducted. RESULTS: A total of nine studies were identified. There was a clear absence of data on parents' own health experience and consultation in general practice. Findings related to navigating general practice on behalf of their child's health including accessibility of general practice and positive and negative experiences of GPs. CONCLUSION: Findings from this review highlight priority areas for research, including further exploration of parents' perspectives on seeking support specifically for their own health concerns, while caring for a child with intellectual disability, to bring more awareness and understanding of the role general practice plays in supporting the health of this carer group. This review also considers implications for clinical services, including tailoring appointments for this patient group as a priority for continuity of care, which may result in improved experiences of general practice and encourage better communication.

Testing adaptive interventions to improve PTSD treatment outcomes in Federally Qualified Health Centers: Protocol for a randomized clinical trial.

BACKGROUND: Posttraumatic stress disorder (PTSD) disproportionately affects low-income individuals and is untreated in 70% of those affected. One third of low-income Americans are treated in Federally Qualified Health Centers (FQHCs), which do not have the capacity to provide all patients with first-line treatments such as Prolonged Exposure (PE). To address this problem, FQHCs could use low-intensity interventions (e.g., Clinician-Supported PTSD Coach: CS PTSD Coach) and medium-intensity interventions (e.g., PE for Primary Care: PE-PC) to treat PTSD with fewer resources. However, some patients will still require high-intensity treatments (e.g., full-length PE) for sustained clinical benefit. Thus, there is a critical need to develop stepped-care models for PTSD in FQHCs. METHOD: We are conducting a Sequential, Multiple Assignment, Randomized Trial (SMART) with 430 adults with PTSD in FQHCs. Participants are initially randomized to CS PTSD Coach or PE-PC. After four sessions, early responders step down to lower frequency interaction within their assigned initial treatment strategy. Slow responders are re-randomized to either continue their initial treatment strategy or step up to Full PE for an additional eight weeks. The specific aims are to test the effectiveness of initiating treatment with PE-PC versus CS PTSD Coach in reducing PTSD symptoms and to test the effectiveness of second-stage strategies (continue versus step-up to Full PE) for slow responders. CONCLUSIONS: This project will provide critical evidence to inform the development of an effective stepped-care model for PTSD. Testing scalable, sustainable sequences of PTSD treatments delivered in low-resource community health centers will improve clinical practice for PTSD.

Lead optimization of aryl hydrocarbon receptor ligands for treatment of inflammatory skin disorders.

Therapeutic aryl hydrocarbon receptor (AHR) modulating agents gained attention in dermatology as non-steroidal anti-inflammatory drugs that improve skin barrier properties. By exploiting AHR's known ligand promiscuity, we generated novel AHR modulating agents by lead optimization of a selective AHR modulator (SAhRM; SGA360). Twenty-two newly synthesized compounds were screened yielding two novel derivatives, SGA360f and SGA388, in which agonist activity led to enhanced keratinocyte terminal differentiation. SGA388 showed the highest agonist activity with potent normalization of keratinocyte hyperproliferation, restored expression of skin barrier proteins and dampening of chemokine expression by keratinocytes upon Th2-mediated inflammation in vitro. The topical application of SGA360f and SGA388 reduced acute skin inflammation in vivo by reducing cyclooxygenase levels, resulting in less neutrophilic dermal infiltrates. The minimal induction of cytochrome P450 enzyme activity, lack of cellular toxicity and mutagenicity classifies SGA360f and SGA388 as novel potential therapeutic AHR ligands and illustrates the potential of medicinal chemistry to fine-tune AHR signaling for the development of targeted therapies in dermatology and beyond.

The Reliability of the GNRB® Knee Arthrometer in Measuring ACL Stiffness and Laxity: Implications for Clinical Use and Clinical Trial Design.

Background: Stability of the knee is dependent on multiple factors including integrity of the anterior cruciate ligament (ACL). Greater knee joint laxity appears to negatively affect dynamic joint function and therefore reliable and valid measures of ACL stiffness and laxity are clinically valuable. Purpose: The aim of this study was to investigate the reliability of the GENOUROB, (GNRB®) knee arthrometer device in measuring both stiffness and laxity of the ACL, and to provide information on sample size calculation for future clinical trials. Study Design: Cross-sectional test-retest study. Method: Twelve healthy student participants (age 24-30 years; 6 females and 6 males) completed testing on two different testing dates. Anterior tibial translation and stiffness were measured using the GNRB® device at forces of 134N and 200N. Reliability analyses were performed using intraclass correlation coefficients (ICC). SEM, MDC, and sample size calculations were also determined. Results: Average anterior tibial displacements of 3.63mm and 5.32mm were found for 134N and 200N of force respectively. ICC values for intra-rater, inter-rater, and test-retest reliability were similar across measures of anterior tibial translation and stiffness, ranging from .72 to .83 (95% CI: .54 to .90). The standard error of measurement (SEM) for anterior tibial stiffness ranged from 3.47 mm/N to 3.76 mm/N. Minimal detectable change (MDC) for test-retest anterior tibial stiffness was 9.6 mm/N. Sample sizes for crossover and parallel design studies were determined. Conclusion: ACL laxity and stiffness measures were found to be reliably obtainable using the GNRB® knee arthrometer under the strict control of the individual's alignment to the device and patellar pad forces. Reliable laxity and stiffness values may assist practitioners in clinical reasoning and the development of individualized ACL rehabilitation programs. Additionally, the sample size calculations presented may aid in future research design. Level of Evidence: 3.

Pediatric Outcomes following Cranial Vault Remodeling with Restricted Use of Postoperative Narcotics: A Retrospective Review.

BACKGROUND: The appropriate use of narcotics for postoperative pain control is controversial because of potential medication-induced complications. The authors sought to determine the effects of narcotics in the pediatric population following cranial vault remodeling operations. METHODS: A retrospective review was performed on 160 consecutive patients who underwent cranial vault remodeling for craniosynostosis. RESULTS: There was a statistically significant difference in total morphine equivalents in the group that experienced no emesis and those with at least one episode of emesis (0.97 morphine equivalents/kg versus 1.44 morphine equivalents/kg; p = 0.05). There was a statistically significant difference in hospital morphine equivalents in the group with documented respiratory events (average, 2.3 morphine equivalents/kg versus 1.3 morphine equivalents/kg in the nonevent group; p = 0.006). The patients who received dexmedetomidine had a trend toward a decrease in hospital narcotic administration with equivalent pain control (1.2 morphine equivalents/kg versus 1.9 morphine equivalents/kg; p = 0.09). There was a statistically significant positive correlation between total morphine equivalents for the hospitalization and hospital stay ( r = 0.27, p = 0.001). The amount of morphine equivalents used in the first 24 hours was also found to be an independent predictor of a respiratory event ( p = 0.002 by multivariate logistic regression). Independent positive predictors of hospital stay were age ( p < 0.001), intensive care unit time ( p < 0.001), and total morphine equivalents for the hospitalization ( p = 0.001) by multivariate analysis with linear regression. CONCLUSION: The authors' study demonstrates improvement in outcomes with decreased use of narcotics, which establishes that there is a need to further explore postsurgical recovery outcomes with multimodal pain control. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

News media and fisheries-independent data reveal hidden impacts of hurricanes.

Climate change will likely intensify hurricane activity in coastal regions. A thorough understanding of hurricane impacts to marine fauna is necessary to prepare for and mitigate potential impacts to social systems dependent upon adjacent fauna. Yet, research attention, conservation funding, and policy all can be biased toward taxa of societal interest, potentially favoring a limited understanding of hurricane impacts. Here, we analyzed the frequency of mentions of taxa in newspaper articles in relation to hurricane activity at three coastal US locations coupled with analysis of long-term fisheries-independent data. While economically important taxa dominate media discourse, we observed long-term hurricane-related abundance declines in ecologically important taxa having little direct human utility. We conclude that there is a potential for research and policy biases related to hurricane impacts. Preparation and mitigation efforts will benefit from researchers and managers making directed efforts to identify and incorporate hurricane sensitive taxa into their work.

Transcript and blood-microbiome analysis towards a blood diagnostic tool for goats affected by Haemonchus contortus.

The Alpine goat (Capra aegagrus hircus) is parasitized by the barber pole worm (Haemonchus contortus). Hematological parameters from transcript and metagenome analysis in the host are reflective of infestation. We explored comparisons between blood samples of control, infected, infected zoledronic acid-treated, and infected antibody (anti-γδ T cells) treated wethers under controlled conditions. Seven days post-inoculation (dpi), we identified 7,627 transcripts associated with the different treatment types. Microbiome measurements at 7 dpi revealed fewer raw read counts across all treatments and a less diverse microbial flora than at 21 dpi. This study identifies treatment specific transcripts and an increase in microflora abundance and diversity as wethers age. Further, F/B ratio reflect health, based on depression or elevation above thresholds defined by the baseline of non-infected controls. Forty Alpine wethers were studied where blood samples were collected from five goats in four treatment groups on 7 dpi and 21 dpi. Transcript and microbiome profiles were obtained using the Partek Flow (St. Louis, Missouri, USA) software suites pipelines. Inflammation comparisons were based on the Firmicutes/Bacteriodetes ratios that are calculated as well as the reduction of microbial diversity.

Topical Vancomycin and Risk of Sternal Wound Infections: A Double-Blind Randomized Controlled Trial.

BACKGROUND: The use of topical vancomycin in the reduction of sternal wound infection (SWI) risk has become a point of contention. The earlier literature consists of observational studies and 1 unblinded trial. Hence, the objective of this study was to assess whether vancomycin reduces the incidence of SWI in a double-blind randomized controlled trial. METHODS: Patients were randomized 1:1 to either vancomycin-soaked (vancomycin) or saline-soaked (control) sponges. The sponges were applied once the sternum was opened and were removed just before sternal closure. Patients were followed up at 3 months and at 1 year postoperatively to determine the incidence of SWI in each group. Results were analyzed according to the modified intention-to-treat principle. RESULTS: This study assessed 1038 patients for eligibility and enrolled 1037 patients. There were 517 patients randomized to the vancomycin group and 520 patients randomized to the control group. Analysis was performed on 1021 patients. At 3 months postoperatively, there was no significant difference in the incidence of SWI between the vancomycin and control groups (2.7% vs 4.1%; P = .23). There was also no significant difference between the vancomycin and control groups in the risk of superficial, deep, and organ-space infections. Similar findings were observed 1 year postoperatively. The most common organism isolated was coagulase-negative Staphylococcus. CONCLUSIONS: The use of vancomycin applied to the sternum during cardiac surgery does not reduce the incidence of SWI.

Trajectories of Heart Activity Across Infancy to Early Childhood Differentially Predict Autism and Anxiety Symptoms in Fragile X Syndrome.

Background: Fragile X syndrome (FXS) is a monogenic disorder characterized by high rates of autism spectrum disorder (ASD) and anxiety. A longstanding "hyperarousal hypothesis" in FXS has argued that ANS dysfunction underpins many symptoms of FXS. However, the developmental onset and trajectory of ANS dysfunction, as well as the consequences of ANS dysfunction on later psychiatric symptoms, remain poorly understood in FXS. Insight into the emergence, trajectory, and consequences of ANS dysfunction across early development in FXS has critical implications for prevention, intervention, and optimal outcomes in both typical and atypical development. This longitudinal study investigated whether and when males with FXS evidence atypical ANS function from infancy through early childhood, and how trajectories of ANS function across infancy and early childhood predict ASD and anxiety symptom severity later in development. Methods: Participants included 73 males with FXS and 79 age-matched typically developing (TD) males. Baseline heart activity was recorded at multiple assessments between 3 and 83 months of age, resulting in 372 observations. General arousal and parasympathetic activity were indexed via interbeat interval (IBI) and respiratory sinus arrhythmia (RSA), respectively. ASD and anxiety symptoms were assessed at 36 months of age or later in a subgroup of participants (FXS n = 28; TD n = 25). Results: Males with FXS exhibited atypical patterns of developmental change in ANS function across infancy and early childhood. As a result, ANS dysfunction became progressively more discrepant across time, with the FXS group exhibiting significantly shorter IBI and lower RSA by 29 and 24 months of age, respectively. Shorter IBI at 24 months and a flatter IBI slope across development predicted elevated anxiety symptoms, but not ASD symptoms, later in childhood in both FXS and TD males. Reduced RSA at 24 months predicted elevated ASD symptoms, but not anxiety symptoms, in both groups. Developmental change in RSA across early development did not predict later anxiety or ASD symptoms. Conclusion: This is the first longitudinal study to examine the "hyperarousal hypothesis" in infants and young children with FXS. Findings suggest that hyperarousal (i.e., shorter IBI, lower RSA) is evident in males with FXS by 24-29 months of age. Interestingly, unique aspects of early ANS function differentially relate to later ASD and anxiety symptoms. General arousal, indexed by shorter IBI that becomes progressively more discrepant from TD controls, predicts later anxiety symptoms. In contrast, parasympathetic-related factors, indexed by lower levels of RSA, predict ASD symptoms. These findings support the "hyperarousal hypothesis" in FXS, in that ANS dysfunction evident early in development predicts later-emerging symptoms of ASD and anxiety. This study also have important implications for the development of targeted treatments and interventions that could potentially mitigate the long-term effects of hyperarousal in FXS.

Ferrimicrobium acidiphilum Exchanges Electrons With a Platinum Electrode via a Cytochrome With Reduced Absorbance Maxima at 448 and 605 nm.

Ferrimicrobium acidiphilum is a Gram-positive member of the Actinobacteria phylum that can respire aerobically or anaerobically with soluble Fe(II) or Fe(III), respectively, in sulfuric acid at pH 1.5. Cyclic voltammetry measurements using intact F. acidiphilum at pH 1.5 produced fully reversible voltammograms that were highly reproducible. The maximum current observed with the anodic peak was considerably less than was the maximum current observed with the cathodic peak. This difference was attributed to the competition between the platinum electrode and the soluble oxygen for the available electrons that were introduced by the cathodic wave into this facultative aerobic organism. The standard reduction potential of the intact organism was determined to be 786 mV vs. the standard hydrogen electrode, slightly more positive than that of 735 mV that was determined for soluble iron at pH 1.5 using the same apparatus. Chronocoulometry measurements conducted at different cell densities revealed that the intact organism remained in close proximity to the working electrode during the measurement, whereas soluble ionic iron did not. When the cyclic voltammetry of intact F. acidiphilum was monitored using an integrating cavity absorption meter, the only small changes in absorbance that were detected were consistent with the participation of a cellular cytochrome with reduced absorbance peaks at 448 and 605 nm. The cytochrome that participated in the exchange of electrons between the intact organism and extracellular solid electrodes like platinum was the same cytochrome whose oxidation was previously shown to be rate-limiting when the organism respired aerobically on extracellular soluble iron.

Accumulating evidence to support the safe and efficacious use of a proprietary blend of capsaicinoids in mediating risk factors for obesity.

Obesity is a significant public health concern, and finding safe and effective means for combating this condition is needed. This study investigates the safety and efficacy of supplementation of a blend of capsaicinoids on weight gain, fat mass, and blood chemistry in a high-fat diet (HFD) model of obesity in mice and on adipocyte differentiation and gene expression in 3T3-L1 preadipocytes. High-fat diet (HFD)-fed mice were treated with a proprietary capsaicinoid concentrate (Capsimax®; OmniActive Health Technologies Ltd., India) and compared to orlistat (ORL) and normal chow-fed mice (NC). Mice fed a high-fat diet showed significantly lower weight gain upon Capsimax® (CAP) administration than their HFD counterparts and similar to that observed with ORL animals. In addition, CAP decreased the high-fat diet-induced increases in adipose tissue and epididymal fat pad mass and hypertrophy after 52 days of treatment. Both the CAP and ORL groups had increased plasma concentrations of leptin. CAP extracts decreased triacylglycerol content in 3T3-L1 preadipocytes and decreased markers of adipogenesis including peroxisome proliferator-activated receptor (PPAR-É£) and fatty acid-binding protein 4 (FABP4). Expression of genes involved in lipogenesis such as stearoyl-CoA desaturase (SCD) and fatty acid synthase (FSN) was decreased by CAP in a dose-dependent manner. Thermogenic genes and markers of brown adipose tissue including uncoupling protein 1 (UCP1) and PR domain-containing 16 (Prdm16) were induced by CAP in the preadipocyte cells. These in vivo and in vitro data support that this proprietary capsaicinoid concentrate reduces weight gain and adiposity at least in part through decreasing lipogenesis and increasing thermogenesis.

Attention Bias and Prodromal Anxiety Symptoms in Toddlers With Fragile X Syndrome and Down Syndrome.

Early identification of behavioral risk markers for anxiety is essential to optimize long-term outcomes in children with neurodevelopmental disorders. This study analyzed attentional avoidance and its relation to anxiety and autism spectrum disorder (ASD) symptomatology during social and nonsocial fear conditions in toddlers with fragile X syndrome (FXS) and Down syndrome (DS). Toddlers with FXS and DS exhibited increased nonsocial attentional avoidance relative to typically developing (TD) toddlers. Attentional avoidance was not related to anxiety symptom severity in any group; however, higher ASD symptom severity was related to more social attentional avoidance in the FXS and TD groups. Findings suggest that there may be different underlying mechanisms driving attentional avoidance across neurodevelopmental disorders.

Early behavioral and physiological markers of social anxiety in infants with fragile X syndrome.

BACKGROUND: Social anxiety is highly prevalent in neurotypical children and children with fragile X syndrome (FXS). FXS is a genetic syndrome that is characterized by intellectual disability and an increased risk for autism spectrum disorder. If social anxiety is left untreated, negative outcomes are highly prevalent later in life. However, early detection of social anxiety is challenging as symptoms are often subtle or absent very early in life. Given the prevalence and impairment associated with childhood social anxiety, efforts have accelerated to identify risk markers of anxiety. A cluster of early features of anxiety have been identified including elevated behavioral inhibition, attentional biases, and physiological dysregulation that index early emerging markers of social anxiety. Infants with FXS provide a unique opportunity to study the earlier predictors of social anxiety. The current study utilized a multi-method approach to investigate early markers of social anxiety in 12-month-old infants with FXS. METHOD: Participants included 32 infants with FXS and 41 low-risk controls, all approximately 12 months old. Parent-reported social behavioral inhibition was recorded from the Infant Behavior Questionnaire (IBQ-R). Direct observations of behavioral inhibition and attention were measured during a stranger approach task with respiratory sinus arrhythmia collected simultaneously. RESULTS: Parent-reported social behavioral inhibition was not significantly different between groups. In contrast, direct observations suggested that infants with FXS displayed elevated behavioral inhibition, increased attention towards the stranger, and a blunted respiratory sinus arrhythmia response. CONCLUSIONS: Findings suggest that infants with FXS show both behavioral and physiological markers of social anxiety at 12 months old using a biobehavioral approach with multiple sources of input. Results highlight the importance of a multi-method approach to understanding the complex early emergent characteristics of anxiety in infants with FXS.

Cardiac Startle Response and Clinical Outcomes in Preschool Children With Fragile X Syndrome and Autism Spectrum Disorder.

Objective: Poor physiological regulation in response to threat is linked to multiple negative developmental outcomes including anxiety, which is highly prevalent and impairing in young children with neurodevelopmental disabilities like fragile X syndrome (FXS) and autism spectrum disorder (ASD). The present study contrasted cardiac startle response in pre-school-aged children with FXS, with and without ASD, to children with non-syndromic ASD (nsASD) and neurotypical controls (NT). The relationship of cardiac startle to non-verbal mental age (NVMA), ASD severity, and parent-reported anxiety was also examined. Method: Four age-matched groups of pre-school children participated including those with FXS without ASD (FXS-Only, n = 21), FXS with ASD (FXS+ASD, n = 17), nsASD (n = 42), and NT children (n = 27). Participants viewed a silent movie during which a single 200 ms 98-decibel white noise burst occurred. Cardiac activity was analyzed for pre-stimulus respiratory sinus arrhythmia (RSA) and the inter-beat intervals (IBI) at the auditory stimulus and 10 s post-stimulus. The Spence Pre-school Anxiety Scale, Autism Diagnostic Observation Schedule-2nd Edition, and Mullen Scales of Early Learning were examined in relation to startle response. Results: The nsASD group demonstrated heightened cardiac activity at the auditory stimulus and 10 s post-stimulus compared to the NT controls. Neither of the FXS groups showed differences from any other group. Higher pre-stimulus RSA was associated with reduced cardiac response across groups, while the relationship between cognitive ability and ASD severity to cardiac response varied between groups. Parent-reported anxiety was not associated with cardiac response for any group. Conclusion: These findings demonstrate group distinctions in cardiac responses to auditory startle. Although FXS and ASD share behavioral characteristics, the nsASD group showed a heightened cardiac startle response compared to the NT group that was not present in the FXS groups with or without ASD. Non-verbal mental age was associated with greater stimulus or post-stimulus reactivity for all groups except the FXS+ASD group, which showed no association between startle response and any clinical outcomes. Increased understanding of the relationship between physiological regulation and clinical outcomes will assist in identifying the timing and targets for effective interventions for individuals with neurodevelopmental disabilities.