Pain Catastrophizing and Functional Disability in Youth with Chronic Pain: An Examination of Indirect Effects.

Pediatric pain conditions are not uncommon and may lead to functional disability. The purpose of this study is to examine indirect effects of pain catastrophizing on functional disability through anxiety, depression, and pain in youth with chronic pain. Participants included 197 youth (144 females, Mage = 14.67 years) with chronic pain conditions. Youth completed self-report measures of pain catastrophizing, depression, anxiety, pain intensity, and functional disability. Caregivers also completed a measure of youth functional disability. Using a cross-sectional design, a multiple mediator model was estimated with pain catastrophizing as the predictor, functional disability as the outcome, and depression, anxiety, and pain intensity as mediators. Results supported a mediation model in which depression (B = 0.1145, SE = 0.0528, Z = 2.1686; B = 0.1512, SE = 0.0585, Z = 2.5846) and pain intensity (B = 0.1015, SE = 0.0422, Z = 2.4052; B = 0.0634, SE = 0.0343, Z = 1.8484) significantly mediated the effects of catastrophizing on child self-report and parent-report functional disability, respectively, while anxiety (B = - 0.0260, SE = 0.0439501, Z = - 0.5923; B = - 0.0637, SE = 0.0552, Z = - 1.1540) did not. Theoretical and clinical applications are discussed.

Fragile X Mental Retardation Protein and Cerebral Expression of Metabotropic Glutamate Receptor Subtype 5 in Men with Fragile X Syndrome: A Pilot Study.

Multiple lines of evidence suggest that a deficiency of Fragile X Mental Retardation Protein (FMRP) mediates dysfunction of the metabotropic glutamate receptor subtype 5 (mGluR5) in the pathogenesis of fragile X syndrome (FXS), the most commonly known single-gene cause of inherited intellectual disability (ID) and autism spectrum disorder (ASD). Nevertheless, animal and human studies regarding the link between FMRP and mGluR5 expression provide inconsistent or conflicting findings about the nature of those relationships. Since multiple clinical trials of glutamatergic agents in humans with FXS did not demonstrate the amelioration of the behavioral phenotype observed in animal models of FXS, we sought measure if mGluR5 expression is increased in men with FXS to form the basis for improved clinical trials. Unexpectedly marked reductions in mGluR5 expression were observed in cortical and subcortical regions in men with FXS. Reduced mGluR5 expression throughout the living brains of men with FXS provides a clue to examine FMRP and mGluR5 expression in FXS. In order to develop the findings of our previous study and to strengthen the objective tools for future clinical trials of glutamatergic agents in FXS, we sought to assess the possible value of measuring both FMRP levels and mGluR5 expression in men with FXS. We aimed to show the value of measurement of FMRP levels and mGluR5 expression for the diagnosis and treatment of individuals with FXS and related conditions. We administered 3-[18F]fluoro-5-(2-pyridinylethynyl)benzonitrile ([18F]FPEB), a specific mGluR5 radioligand for quantitative measurements of the density and the distribution of mGluR5s, to six men with the full mutation (FM) of FXS and to one man with allele size mosaicism for FXS (FXS-M). Utilizing the seven cortical and subcortical regions affected in neurodegenerative disorders as indicator variables, adjusted linear regression of mGluR5 expression and FMRP showed that mGluR5 expression was significantly reduced in the occipital cortex and the thalamus relative to baseline (anterior cingulate cortex) if FMRP levels are held constant (F(7,47) = 6.84, p < 0.001).These findings indicate the usefulness of cerebral mGluR5 expression measured by PET with [18F]FPEB and FMRP values in men with FXS and related conditions for assessments in community facilities within a hundred-mile radius of a production center with a cyclotron. These initial results of this pilot study advance our previous study regarding the measurement of mGluR5 expression by combining both FMRP levels and mGluR5 expression as tools for meaningful clinical trials of glutamatergic agents for men with FXS. We confirm the feasibility of this protocol as a valuable tool to measure FMRP levels and mGluR5 expression in clinical trials of individuals with FXS and related conditions and to provide the foundations to apply precision medicine to tailor treatment plans to the specific needs of individuals with FXS and related conditions.

Brain Oxygen Extraction and Metabolism in Pediatric Patients With Sickle Cell Disease: Comparison of Four Calibration Models.

Sickle cell disease (SCD) is an inherited hemoglobinopathy with an increased risk of neurological complications. Due to anemia and other factors related to the underlying hemoglobinopathy, cerebral blood flow (CBF) increases as compensation; however, the nature of alterations in oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen (CMRO2) in SCD remains controversial, largely attributed to the different calibration models. In addition, limited studies have been done to investigate oxygen metabolism in pediatric patients. Thus, this study used a non-invasive T2-based MR oximetry, T2-Relaxation-Under-Spin-Tagging (TRUST) MRI, to measure oxygen homeostasis in pediatric patients with SCD using four different calibration models and examined its relationship to hematological measures. It was found that, compared with controls, SCD patients showed an increased CBF, unchanged total oxygen delivery and increased venous blood T2. The results of OEF and CMRO2 were dependent on the calibration models used. When using sickle-specific, hemoglobin S (HbS) level-dependent calibration, there was a decreased OEF and CMRO2, while the bovine model showed an opposite result. OEF and CMRO2 were also associated with hemoglobin and HbS level; the direction of the relationship was again dependent on the model. Future studies with in vivo calibration are needed to provide more accurate information on the T2-Y v relationship.

Suicide Risk Screening in Pediatric Outpatient Neurodevelopmental Disabilities Clinics.

OBJECTIVE: The purpose of this study was to describe the implementation of universal suicide risk screening in pediatric neurodevelopmental disabilities (NDD) medical clinics, analyze demographic and clinical characteristics of eligible patients, describe outcomes of positive screenings, and describe factors that influenced participation in screenings. METHODS: A suicide risk screening protocol was developed and implemented for medical clinic patients aged 8 to 18 years. Registered nurses screened patients using the "Ask Suicide-Screening Questions" tool during triage. Positive screenings were referred for further assessment and mental health management. Demographics and clinical data were extracted from medical records using retrospective chart reviews. RESULTS: During the 6-month study period, 2961 individual patients presented for 5260 screening eligible patient visits. In total, 3854 (73.3%) screenings were completed with 261 (6.8%) positive screenings noted. Screenings were declined in 1406 (26.7%) visits. Parents of children with cognitive impairments were more likely to decline screening. Clinics serving children with autism spectrum disorder had higher rates of positive screenings compared with all other clinic attendees. Seventy-two of 187 children (38.5%) with positive screenings were identified and referred to outpatient mental health referrals. Seven (2.5%) of these children required acute psychiatric treatment. CONCLUSION: Routine screening, identification of increased suicide risk, and referral to mental health care among children with NDD are feasible. It remains unclear whether variation in rates among youth with and without NDD may indicate true differences in suicide risk or cognitive impairments or reflect psychiatric comorbidities. High rates of declined participation may have influenced identification of children with NDD and suicide risk. Preliminary findings identified groups of children with NDD at heightened risk for suicidal ideation and behavior. Further research is needed to assess the validity of suicide risk screening tools in children with neurodevelopmental disorders.

Cerebral Expression of Metabotropic Glutamate Receptor Subtype 5 in Idiopathic Autism Spectrum Disorder and Fragile X Syndrome: A Pilot Study.

Multiple lines of evidence suggest that dysfunction of the metabotropic glutamate receptor subtype 5 (mGluR5) plays a role in the pathogenesis of autism spectrum disorder (ASD). Yet animal and human investigations of mGluR5 expression provide conflicting findings about the nature of dysregulation of cerebral mGluR5 pathways in subtypes of ASD. The demonstration of reduced mGluR5 expression throughout the living brains of men with fragile X syndrome (FXS), the most common known single-gene cause of ASD, provides a clue to examine mGluR5 expression in ASD. We aimed to (A) compare and contrast mGluR5 expression in idiopathic autism spectrum disorder (IASD), FXS, and typical development (TD) and (B) show the value of positron emission tomography (PET) for the application of precision medicine for the diagnosis and treatment of individuals with IASD, FXS, and related conditions. Two teams of investigators independently administered 3-[18F]fluoro-5-(2-pyridinylethynyl)benzonitrile ([18F]FPEB), a novel, specific mGluR5 PET ligand to quantitatively measure the density and the distribution of mGluR5s in the brain regions, to participants of both sexes with IASD and TD and men with FXS. In contrast to participants with TD, mGluR5 expression was significantly increased in the cortical regions of participants with IASD and significantly reduced in all regions of men with FXS. These results suggest the feasibility of this protocol as a valuable tool to measure mGluR5 expression in clinical trials of individuals with IASD and FXS and related conditions.

Reduced Expression of Cerebral Metabotropic Glutamate Receptor Subtype 5 in Men with Fragile X Syndrome.

Glutamatergic receptor expression is mostly unknown in adults with fragile X syndrome (FXS). Favorable behavioral effects of negative allosteric modulators (NAMs) of the metabotropic glutamate receptor subtype 5 (mGluR5) in fmr1 knockout (KO) mouse models have not been confirmed in humans with FXS. Measurement of cerebral mGluR5 expression in humans with FXS exposed to NAMs might help in that effort. We used positron emission tomography (PET) to measure the mGluR5 density as a proxy of mGluR5 expression in cortical and subcortical brain regions to confirm target engagement of NAMs for mGluR5s. The density and the distribution of mGluR5 were measured in two independent samples of men with FXS (N = 9) and typical development (TD) (N = 8). We showed the feasibility of this complex study including MRI and PET, meaning that this challenging protocol can be accomplished in men with FXS with an adequate preparation. Analysis of variance of estimated mGluR5 expression showed that mGluR5 expression was significantly reduced in cortical and subcortical regions of men with FXS in contrast to age-matched men with TD.

Discrepancies in Assessing Symptoms of Depression in Adolescents With Diabetes Using the Patient Health Questionnaire and Semi-Structured Interviews.

Adolescents with diabetes have a higher prevalence of depression compared with their peers. The American Diabetes Association recommends routine mental health screening for youth with diabetes. This screening is often conducted through accessible and free depression screeners, such as the nine-item Patient Health Questionnaire (PHQ-9). Although the PHQ-9 has been validated for use in adolescents and with other medical conditions, it has yet to be validated for use in pediatric diabetes. This study evaluated adolescents' depression symptom endorsement through retrospective review of PHQ-9 screening and semi-structured interviews with a mental health provider in a multidisciplinary diabetes clinic (patients with type 1 or type 2 diabetes). Adolescent participants (n = 96) screened during one to three separate visits (n = 148) endorsed some depressive symptoms in 56% of visits (n = 84) and moderate to severe symptoms in 6% of visits on the PHQ-9. Approximately 95% of study participants did not meet the clinic cutoff for further evaluation, but greater rates of depression were endorsed in youth with type 1 diabetes. Low mood was endorsed at a higher rate during a semi-structured interview with embedded mental health providers than on the PHQ-9. Symptoms specific to low mood, including anhedonia, sleep disturbance, concentration disturbance, motor disturbance, and thoughts of death/self-harm, were more frequently endorsed on the PHQ-9 than during the interview. Although the PHQ-9 is a good screening tool, the availability of mental health providers in diabetes clinics is important to address specific endorsed symptoms and place them in perspective based on specialized training. Until more definitive research is available on the sensitivity and specificity of this measure in this population and setting, a two-part screening approach that includes both the screening questionnaire and a brief semi-structured interview is warranted.

Anomalous Brain Development Is Evident in Preschoolers With Attention-Deficit/Hyperactivity Disorder.

OBJECTIVES: Attention-deficit/hyperactivity disorder (ADHD) is a common neurological disorder with symptom onset early in childhood. Growing evidence suggests anomalous brain development across multiple brain regions is evident in school-aged children; however, few studies have examined whether such differences are notable in the preschool years when symptom onset typically occurs. METHODS: High resolution anatomical (MPRAGE) images and cognitive and behavioral measures were analyzed in a total of 90 medication-naïve preschoolers, ages 4-5 years (52 with ADHD, 38 controls; 64.4% boys). RESULTS: Results revealed reductions in bilateral frontal, parietal, and temporal lobe gray matter volumes in children with ADHD relative to typically developing children, with largest effect sizes noted for right frontal and left temporal lobe volumes. Examining frontal lobe sub-regions, the largest between group effect sizes were evident for left orbitofrontal cortex, left primary motor cortex (M1), and left supplementary motor complex (SMC). ADHD-related reductions in specific sub-regions (left prefrontal, left premotor, left frontal eye field, left M1, and right SMC) were significantly correlated with symptom severity, such that higher ratings of hyperactive/impulsive symptoms were associated with reduced cortical volumes. CONCLUSIONS: These findings represent the first comprehensive examination of cortical volume in preschool children with ADHD, providing evidence that anomalous brain structure in ADHD is evident very early in development. Furthermore, findings set the stage for developing our understanding of the way in which developmental trajectories of anomalous brain development are associated with the unfolding of symptoms in childhood ADHD. (JINS, 2018, 24, 531-539).

Multicomponent cognitive-behavioural intervention to improve sleep in adolescents: a multiple baseline design.

BACKGROUND: Adolescents are prone to sleep problems that have unique developmental aspects and contribute to physical, emotional, and behavioural problems. AIMS: This study evaluated an individualized, multicomponent intervention that considered developmental factors, and promoted age-appropriate autonomy in three adolescent females with disrupted sleep. METHOD: Adolescents recorded sleep data on daily logs. A nonconcurrent multiple baseline design was used to evaluate a cognitive-behavioural intervention including sleep hygiene training, bedtime routine development, cognitive restructuring, relaxation training, stimulus control, sleep restriction, bedtime fading, and problem-solving, along with clinically indicated individualization. RESULTS: Outcomes demonstrated clinically meaningful improvements and decreased variability in sleep parameters following intervention. Each participant's sleep log data indicated improvement in, or maintenance of, adequate total sleep time (TST), decreased sleep onset latency (SOL), improved sleep efficiency (SE), improvement in time of sleep onset, and decreased or continued low frequency of night awakenings (NA). Anecdotally, adolescents and parents reported improvement in daytime functioning, coping, and sense of wellbeing. CONCLUSIONS: These cases highlight the potential for cognitive-behavioural interventions to facilitate healthy sleep in adolescents with challenging sleep problems.

Technical tips: performing EEGs and polysomnograms on children with neurodevelopmental disabilities.

Electroencephalograms (EEGs) and polysomnograms (PSGs) are critical and frequently ordered tests in the care of children with neurodevelopmental disabilities (NDD). Performing studies with this population can be very intimidating, given that the referral reasons and seizure types can be unique, and children with NDD may have any combination of behavioral or sensory challenges that can make it difficult to successfully complete a study. This article presents a variety of strategies that can be used to overcome these challenges through good preparation, patience, caregiver involvement, effective behavioral management techniques, and education about the medical aspects of EEG/ PSG in NDD. This Technical Tips article features ideas and experiences from an EEG/PSG technologist, two board-certified child neurologists (one who is further certified in Clinical Neurophysiology, while the other is further certified in Sleep Medicine), and two behaviorally trained pediatric psychologists.

Distraction, exposure therapy, counterconditioning, and topical anesthetic for acute pain management during needle sticks in children with intellectual and developmental disabilities.

A behavior therapy approach for obtaining cooperation during needle sticks was provided to 8 pediatric patients with intellectual and developmental disabilities. Therapy was provided during mock needle sticks. Hand lotion was applied to simulate topical anesthetic. Distracting activities established relaxation while needle stick materials were gradually introduced. Positive reinforcement was provided for cooperation. Behavioral distress was ignored, blocked, or redirected. After cooperating with mock needle sticks, needle sites were prepared with topical anesthetic (EMLA), then therapists and medical staff implemented the behavioral protocol while completing the actual needle stick(s). Observational measures of cooperation and interfering were obtained. Results were replicated across 8 children and evaluated using paired samples t tests. Initially, all children were uncooperative with needle sticks. With treatment, behavioral distress decreased, and patients cooperated with mock and actual needle sticks. Results support the effectiveness of behavior therapy for promoting cooperation in children with intellectual and developmental disabilities during needle sticks.

Using behavioral interventions to assist with routine procedures in children with cystic fibrosis.

Routine cystic fibrosis (CF) medical care includes invasive procedures that may be difficult for young children and adolescents to tolerate because of anxiety, concern with health status, or unfamiliarity with the performed tasks. A growing body of pediatric psychology literature suggests that behavior therapy can effectively increase patient cooperation with stressful medical procedures such as tracheostomy care and needle sticks. Throat cultures are obtained at least quarterly in the outpatient setting or more frequently if a CF patient develops respiratory symptoms. Obtaining a throat culture from an anxious and uncooperative child poses a significant challenge for physicians, since the child may demonstrate emotional distress and avoidant behavior that disrupts efficient specimen collection during a routine clinic visit. The use of behavioral interventions, such as relaxation exercises, diaphragmatic breathing, differential reinforcement, gradual exposure, and systematic desensitization, is beneficial in addressing this commonly encountered problem in CF care. This case series describes the implementation of a behavioral therapy protocol utilizing two interventions, gradual exposure and systematic desensitization, in two young CF patients for the treatment of behavioral distress with routine throat cultures. The behavioral interventions were simple and transferred easily from mock procedures to actual specimen collection. Moreover, these cases highlight the important roles of the pediatric psychology staff on a comprehensive multidisciplinary CF care team to improve patient cooperation with routine clinic procedures and the medical treatment regimen overall.

Interdisciplinary behavioral rehabilitation of pediatric pain-associated disability: retrospective review of an inpatient treatment protocol.

OBJECTIVE: A biopsychosocial model was used to treat pain-associated disability in children and adolescents. We assessed the clinical outcomes of children and adolescents (8-21 years of age) with pain-associated disability who were treated in an interdisciplinary inpatient rehabilitation program which included physical, occupational, and recreational therapy, medicine, nursing, pediatric psychology, neuropsychology, psychiatry, social work, and education. Psychological treatment emphasized cognitive-behavioral intervention for pain and anxiety management, and behavioral shaping to increase functioning. METHODS: We conducted a retrospective chart review of 41 consecutive patients. School attendance, sleep, and medication usage were assessed at admission and discharge; functional disability and physical mobility were assessed at admission, discharge, and 3-month follow-up. RESULTS: As a group, significant improvements were observed in school status, sleep, functional ability, physical mobility, and medication usage. CONCLUSION: Findings support the efficacy of an inpatient interdisciplinary behavioral rehabilitation approach to the treatment of pain-associated disability in pediatric patients.

Behavior management for children and adolescents with acquired brain injury.

Behavioral problems such as disinhibition, irritability, restlessness, distractibility, and aggression are common after acquired brain injury (ABI). The persistence and severity of these problems impair the brain-injured individual's reintegration into family, school, and community life. Since the early 1980s, behavior analysis and therapy have been used to address the behavioral sequelae of ABI. These interventions are based on principles of learning and behavior that have been robustly successful when applied across a broad range of other clinical populations. Most of the research on behavioral treatment after ABI has involved clinical case studies or studies employing single-subject experimental designs across a series of cases. The literature supports the effectiveness of these interventions across ages, injury severities, and stages of recovery after ABI. Recommended guidelines for behavior management include: direct behavioral observations, systematic assessment of environmental and within-patient variables associated with aberrant behavior, antecedent management to minimize the probability of aberrant behavior, provision of functionally equivalent alternative means of controlling the environment, and differential reinforcement to shape positive behavior and coping strategies while not inadvertently shaping emergent, disruptive sequelae. This package of interventions requires direction by a highly skilled behavioral psychologist or therapist who systematically monitors target behavior to evaluate progress and guide treatment decisions. A coordinated multisite effort is needed to design intervention protocols that can be studied prospectively in randomized controlled trials. However, there will continue to be an important role for single subject experimental design for studying the results of individualized interventions and obtaining pilot data to guide subsequent randomized controlled trails.

Comparison of Two Brief Parent-Training Interventions for Child Distress During Parent-Administered Needle Procedures.

This randomized clinical trial employed a 2-group (general child behavior management training vs. distraction for pain management training) design across repeated parent-administered needle procedures. Forty-seven children with a chronic illness requiring recurrent injections were observed at baseline and 2 intervention sessions. Videotaped observations of parent-child interactions were coded for child behavioral distress and parents' use of behavior management strategies. Across groups, many children displayed minimal to no distress at baseline. Among participants with significant distress, neither intervention group displayed consistently decreased procedural distress or increased use of child behavior management strategies.

Behavioral Approaches to Training Developmentally Disabled Children for an Overnight EEG Procedure.

Smith-Lemli-Opitz syndrome (SLOS) is a genetic syndrome associated with multiple congenital malformations, mental retardation, and autism spectrum behaviors. This clinical protocol was part of a larger study investigating the effects of a cholesterol-lowering medication for SLOS patients. Behavioral therapists were consulted to facilitate participants' cooperation with an overnight electroencephalogram (EEG). Seventeen children participated in one 1-hour training session of a mock EEG. Behavioral methods included task analysis, differential reinforcement, and escape extinction. Descriptive data reveal low cognitive and adaptive functioning. Fifty three percent of children tolerated all steps of the training procedure and 88% of participants tolerated all of the actual EEG procedure. Behavioral methods of training children may be an effective preparation for EEG procedures for children with SLOS. This study indicates that sedation, anesthesia, or restraints are not necessary to accomplish EEG testing of children with SLOS. Results may generalize to children with a range of disabilities.

Interdisciplinary behavioral intervention for life-threatening obesity in an adolescent with Prader-Willi syndrome - a case report.

OBJECTIVE: To demonstrate interdisciplinary behavioral rehabilitation for life-threatening obesity in an adolescent female with Prader-Willi syndrome. METHODS: Body Mass Index (BMI), supplemental oxygen requirement, mobility, and tantrums were documented. A 600 kcal per day diet, physical therapy, and exercise were implemented in an inpatient setting. A behavioral program was employed by an interdisciplinary team to ensure dietary adherence and to increase patient compliance with therapy demands. Family caregivers were trained and continued the intervention at home. RESULTS: Important improvements were achieved and maintained including weight loss, decreased need for supplemental oxygen, greater exercise tolerance, and fewer tantrums. The patient's BMI decreased from 84.3 to 59.8 during inpatient treatment, and to 41.0 at last follow-up. CONCLUSIONS: Behavioral rehabilitation can be beneficial and potentially life saving for morbidly obese children with Prader-Willi syndrome, and perhaps for other obese youth with developmental or behavioral problems.

Behavioral intervention to increase compliance with electroencephalographic procedures in children with developmental disabilities.

The EEG, or electroencephalogram, is a neurophysiological technique used to detect and record electrical activity in the brain. It is critical to the diagnosis and management of seizure disorders, such as epilepsy, as well as other neurological conditions. The EEG procedure is often not well tolerated by children with developmental disabilities because of anxiety about unfamiliar equipment, difficulty inhibiting motion, and tactile defensiveness. The inability of children with developmental disabilities to tolerate an EEG procedure is especially problematic because the incidence of epilepsy is considerably higher in children with disabilities. This clinical outcome study sought to determine the efficacy of using behavioral intervention to teach children with developmental disorders to cooperate with an EEG procedure. The behavioral training employed modeling, counterconditioning, escape extinction, and differential reinforcement-based shaping procedures. Results indicated that behavioral training is successful in promoting EEG compliance without restraint, anesthesia, or sedation.

Children with seizures exhibit preferences for foods compatible with the ketogenic diet.

Although highly effective for the treatment of intractable epilepsy, the ketogenic diet is not always included in the treatment option hierarchy presented to families, in part due to perceptions that children will find the high-fat/low-carbohydrate regimen unpalatable. This study assessed if children with seizures exhibit food preferences compatible with the diet, as well as if caregivers were accurate in predicting preferences. Children aged 2-17, with (n=29) and without (n=30) a history of seizures, participated in a paired choice food preference assessment while parents estimated child preferences verbally. Children with seizures exhibited significantly higher preferences for fat versus carbohydrate foods compared with controls, and parents demonstrated low accuracy. Future studies could use similar assessment methods to prospectively track whether such preferences predict diet compliance and/or efficacy. Research into the underlying metabolic basis for this preference and possible related neurophysiological mechanisms in seizure etiology and treatment is warranted.