Search

Introduction Up to 17%–20% of pediatric patients with chronic pain are prescribed opioid pharmacotherapy and face an increased risk of opioid misuse in adulthood. Little is known about the way clinical presentation may influence which children with chronic pain are prescribed opioids. This study examines the associations between child's and caregiver's report of child's pain, physical function, and socioemotional indices with opioid prescriptions in pediatric patients initiating treatment for chronic pain. Methods Participants were 1,155 pediatric patients (71.26% female, n=823) aged 8–17 years and 1 of their caregivers (89% mothers) who presented for evaluation at a tertiary care pediatric pain clinic. Data were collected from 2015 to 2019 and analyzed in 2020. Results Binary logistic regression analyses investigated the relative contribution of child's demographic, pain, and Patient-Reported Outcome Measurement Information System measures to opioid prescription status; separate models were conducted for child's and caregiver's report. Across child and caregiver models, findings were that child's age (older), pain duration (longer; child's report only), and increased physical limitations (mobility challenges and pain interference; caregiver's report only) were the most salient clinical correlates of positive opioid status. Contrary to the existing literature on adults with chronic pain, socioemotional indices (anxiety, depression, peer functioning) were nonsignificant. Conclusions A greater understanding of how clinical presentation may relate to prescribed opioid pharmacotherapy informs the field's conceptualization of the sequelae of opioid use and misuse in the context of pediatric chronic pain.

Targeting individually based psychosocial profiles when treating children with chronic pain and their families is key to effective behavioral health intervention and in line with tenants of precision medicine. Extant research is primarily driven by variable-centered models that focus on broad, group-level differences. The current study adopts a person-centered approach, latent profile analysis (LPA), to identify patient subgroups. Cross-sectional data are presented from 366 children (8–17 years; M = 14.48; standard deviation = 2.36) with chronic pain and a primary caregiver (94% mothers). LPA indicator variables were self-reported: fatigue, internalizing symptoms, pain catastrophizing, and pain acceptance; and parent-reported: pain catastrophizing and responses to child pain. One-way analyses of variances examined the effect of profiles on child age, pain, and function. LPA identified a 4-profile solution. Class 1 (12%) demonstrated the lowest scores (conveying least risk) across 5 of 6 factors. Class 4 (37%) had the highest scores (conveying greatest risk) across all factors. Classes 2 (12%) and 3 (39%) demonstrated more variability across domains. Results revealed significant effects of profile based on child age, pain, and function. This study highlights differential presentation of treatment-modifiable domains within a large sample. LPA methodology is showcased to potentially facilitate clinical conceptualizations and tailored approaches to intervention in pediatric chronic pain. Perspective This article presents a methodological and statistical approach that may be beneficial to better assess individual profiles of pediatric pain functioning. Tools that allow providers to better match patient presentation and intervention are in line with the tenants of precision medicine and may ultimately serve to improve child outcomes.

Theoretical models and evidence increasingly identify chronic pain as a family issue. To date, much of this work has focused on risk conferred by parental chronic pain status despite evidence suggesting parent mental illness and non-pain-related chronic illness may also contribute to poorer chronic pain outcomes in children. This study is the first to test interpersonal fear avoidance processes as possible mechanisms through which parent health (mental and physical) influences pediatric chronic pain functioning. We used structural equation models to test such an integrative model using cross-sectional data from a large clinical registry of 448 dyads of patients aged between 8 and 18 years (M = 14.57 years; SD = 2.38; 327 females) with mixed chronic pain and their parents (403 mothers). As expected, poorer parent global health was indirectly related to greater child pain interference through higher parent pain catastrophizing, and then through greater parent protective behaviors and child pain catastrophizing. The model demonstrated excellent fit to the data (χ[5] = 5.04, ns; χ/df = 1.01; comparative fit index = 1.00, root mean square error of approximation = 0.004 [90% confidence interval = 0.000 to 0.066]). Exploratory multiple-group comparison structural equation model revealed moderation of specific model paths based on child age group (8- to 12-year-olds vs 13- to 18-year-olds) and parent pain status (present vs absent). This study integrates family models of pain with the interpersonal fear avoidance model to extend our mechanistic understanding of parental physical and mental health contributors to pediatric chronic pain.

Despite well-documented pain disparities among adults from non-White and Hispanic groups, less is known about pain disparities in non-White and Hispanic pediatric populations.We compare pain and related psychosocial factors at the individual (pain intensity, pain interference, pain catastrophizing, co-occurring symptoms), social (peer relations), and systemic (health insurance) levels among Hispanic and Non-Hispanic White (NHW) youth with chronic pain.Eight hundred thirty-seven (71.4% female) Hispanic (n = 268, 32%) and NHW (n = 569, 68%) youth ages 8 to 17 years (M = 14.00; SD = 2.54) completed a survey at their initial visit to a pain clinic. Independent sampleHispanic youth reported higher levels of pain intensity (Hispanic youth report higher pain levels than NHW counterparts and lower likelihood of having private insurance. Pain and psychosocial factors correlate differently among the 2 groups highlighting a need to better understand the chronic pain experiences of diverse youth because models derived primarily from NHW populations may not generalize across ethnic and racial groups.

Objectives Pain catastrophizing is an important predictor of pain-related outcomes. Caregiver and child levels of catastrophizing about child chronic pain are associated cross-sectionally, yet predictive associations testing interpersonal influences within caregiver-child dyads are lacking. The present study tested caregiver and child influences on partner catastrophizing about child pain over a period of 1 month following initiation of interdisciplinary pain treatment and examined whether the change in pain catastrophizing was associated with child pain interference. Materials and methods A total of 113 caregiver-child dyads (Mage=14.41) completed measures at the time of initiating care at a pediatric tertiary outpatient pain management clinic (baseline) and ∼1 month later. Caregivers and children independently reported on catastrophizing about child pain and child pain interference at baseline and 1-month follow-up. Results Caregiver and child pain catastrophizing decreased over 1 month following initial interdisciplinary pain evaluation, with average scores remaining in the moderate to high range. Change in caregiver, but not child, catastrophizing about child pain was predicted by partner baseline pain catastrophizing. Decreases in catastrophizing about child pain were associated with within-person improvement in ratings of child pain interference. Discussion In the short period following initial pain evaluation, caregivers and children evidenced reductions in pain catastrophizing, which were associated with increased child function. Findings highlight the important role of child cognitive-affective responses to pain in influencing caregiver catastrophizing about child pain. Understanding the individual contributions children and caregivers make to interpersonal pain processes will inform future family-level clinical interventions.

Patient Reported Outcomes (PROs) are utilized in clinical registries and trials, necessitating development of benchmarks to enhance interpretability. This study aimed to 1) examine if PROMIS measures administered via computer adaptive testing (CAT) were responsive to change, and 2) highlight one method of assessing clinically significant change for youth seen in a tertiary pain clinic. Clinically significant change was achieved if patients had significantly reliable pre-to-post-changes greater than Reliable Change Index (RCI) value and reported decreased symptoms by at least one severity level (e.g., moderate to mild). Participants were 328 youth (8-17 years old) seen in a tertiary pediatric pain management clinic. Small to moderate effect sizes were noted across PROMIS measures (except Peer Relations). Reliable magnitudes of change were estimated for this sample as approximately 6 point reduction for Pain Interference and Mobility, 9 for Fatigue, and 11 for Anxiety and Depression. Depending on the measure, 10 to 24% were categorized as improved, 3 to 6% as deteriorated, and 68 to 81% were either not clinically elevated at baseline or remained unchanged at 3 months. Overall, PROMIS CAT measures demonstrated responsiveness to change over time. Estimation of clinically significant change offers preliminary yet rigorous benchmarks for evaluating treatment response and sets the stage for understanding treatment effects. Perspective This study assesses responsiveness of CAT administered PROMIS measures and highlights one methodological approach of presenting clinical significance for assessing treatment outcomes in pediatric chronic pain. These benchmarks will allow clinicians and researchers to evaluate treatment response utilizing PROs while allowing for a deeper understanding of treatment effects.

Complex regional pain syndrome (CRPS) is a pain condition characterized by regional pain (often extremity pain) that is disproportionate in intensity to the original injury/illness. Cooccurring symptoms are autonomic and inflammatory in nature and may include swelling, temperature change, skin color changes, and motor changes, among others. Optimal treatment for CRPS utilizes a multidisciplinary approach, incorporating a team of specialty healthcare providers. Behavioral health interventions are a key domain of multidisciplinary care and have been shown to reduce functional impairments, pain, and comorbid psychological symptoms associated with CRPS. Behavioral health interventions are rooted in a biopsychosocial framework that accounts for biological, psychological, social, and environmental factors that influence pain and pain-related disability. The overarching aim of this chapter is to present an overview of evidence-based behavioral health treatments for chronic pain, as applied to CRPS, and consider promising directions for the field.

Objectives Valid and efficient assessment of patient-reported outcomes remains a priority to guide pain treatment and research. PROMIS pediatric self-report and parent proxy measures offer feasible and rigorous evaluation of functioning in children with chronic conditions, including pain. A key challenge is determining the usefulness of multisource information from children and caregivers for understanding pain and function. Our primary aim examined child-caregiver agreement across child functioning domains. Our secondary aim examined child and caregiver factors associated with the child-caregiver agreement. Materials and methods A sample of 806 children with chronic pain (Mage=14.50 y; 72% female individuals) and a caregiver (Mage=45.82 y; 85% mothers) completed PROMIS pediatric self-report and parent proxy measures of anxiety, depression, fatigue, pain interference, and mobility before intake in an interdisciplinary outpatient pediatric chronic pain program. Results The agreement was poor to good depending on the evaluation method (effect size, intraclass correlation, and clinical significance interpretation). Caregivers generally reported worse child symptoms across domains compared with child self-report. The greatest discrepancy was observed for child anxiety, pain interference, and peer relations, with the greatest agreement for child mobility. The greater caregiver-child discrepancy was found for younger children, girls, with a higher child or caregiver pain catastrophizing, and poorer caregiver physical or mental health. Discussion Findings are discussed within the interpersonal context of pain and indicate the relevance of both child and caregiver perspectives to personalize chronic pain assessment and treatment. Findings can be used by clinicians and researchers to guide whether and how to integrate multi-informant reports about child chronic pain functioning.

This theoretical review aims to present the limited findings on traumatic stress and pain in children and adolescents, highlight recent discoveries regarding neurobiological processes, and suggest an alternative stress-health perspective in the future study and conceptualization of pediatric pain and traumatic stress based on results. Current literature highlights a positive correlation between pain and trauma symptoms in youth and suggests a complex relationship that may have mutually maintaining dynamics and intertwined physiological processes. Developmentally sensitive, longitudinal, process-oriented designs assessing neurobiological alterations and stress responses should be utilized in the examination of the trauma-pain relationship. Such investigations may provide a more unified explanation of the relationship between chronic pain and traumatic stress.

Pain-related fear and avoidance are increasingly demonstrated to play an important role in adult and childhood chronic pain. The Fear of Pain Questionnaire for Children (FOPQC) is a 24-item measure of pain-related fear-avoidance in youth that has demonstrated good indices of reliability and validity, treatment responsiveness, and associations with brain circuitry alterations. This study describes the development and psychometric examination of the FOPQC-SF, a short form of the original measure. We selected 10 items for the short form that best represented the content and 2-factor (fear and avoidance) structure of the original measure from a cohort of 613 youth (Mage = 14.7 years) with chronic pain. Next, confirmatory factor analyses from a second sample of 526 youth (Mage = 14.7 years) with chronic pain who completed the FOPQC-SF supported the original 2-factor model but indicated that one item should be moved to the avoidance subscale. The FOPQC-SF demonstrates strong internal consistency and moderate-to-strong construct and criterion validity. The 3-month test-retest reliability estimates (N = 94) were strong, and there was preliminary evidence of responsivity to change. To aid integration into intervention trials and clinical practice, we provide clinical reference points and a criterion to assess reliable change. The short form could be used for rapid identification of pain-related fear and avoidance in youth during clinic evaluations, and is optimized for clinical registries.

Pain is an important, useful component of the childhood experience; however, for some youth who experience discomfort chronically, pain can become a debilitating symptom that limits multiple aspects of daily living, including in the school environment. Pain is a biopsychosocial experience that is affected by behavioral, cognitive, affective, sociocultural, and neurosensory factors, as well as contextual factors (family, peers, school). School-based professionals working with students with chronic pain are encouraged to closely collaborate with the child’s multidisciplinary providers outside the school system to promote optimal functioning and wellness in the child across settings. This chapter presents information about several common pediatric pain conditions and then reviews intervention and management strategies for children with chronic pain disorders. It also discusses school-related considerations for the school-based professional and includes a list of useful resources and handouts to assist with education and intervention in the school setting.

Objectives Both pediatric and parent pain catastrophizing and pain acceptance are key factors associated with pediatric pain outcomes; however, the interactive effects of these factors within the parent-child dyad have yet to be tested. The aims of this study were to examine: (1) the mediating role of child catastrophizing between parent catastrophizing and child outcomes (pain interference and mobility), (2) the mediating role of child acceptance between parent acceptance and child outcomes, and (3) whether child acceptance buffers the relation between parent catastrophizing and child catastrophizing, which in turn impacts child outcomes. Materials and methods Cross-sectional data from 324 youth with chronic pain ages 10 to 17 years (mean age=14.72, [SD=2.12]; 73.1% female; 59% Caucasian) and their parents were collected. Participants completed measures assessing pediatric Patient-Reported Outcome Measurement Information System (PROMIS) domains (mobility and pain interference), pain catastrophizing, pain acceptance, and child pain intensity. Mediation was conducted via 1000-draw bootstrap-adjusted analyses in Mplus. Results Parent pain catastrophizing was indirectly associated with child pain interference via child catastrophizing but was not associated with mobility difficulties in the mediation model. Parent pain acceptance was indirectly associated with both child pain interference and mobility via child acceptance. We did not find evidence of child acceptance-buffering parent and child pain catastrophizing. Discussion The findings of this study highlight the need for caregiver involvement in multidisciplinary treatments to mitigate risk and enhance resilience in youth with chronic pain.

Parental health, beliefs and behaviors influence pediatric pain experiences and treatment outcomes. There is increasing acknowledgment of pain disparities in underrepresented ethnic groups and growing understanding of social and economic factors (SEFs) that affect pain. Less is known about SEFs’ impact on caregivers and whether the presence of multiple SEFs increases risk of disparities. The present study assesses 1) disparities by ethnicity and insurance status in mental health (MH), physical health (PH), pain catastrophizing (PC) and protective behaviors (PB) of caregivers of children with pain, and 2) whether insurance status moderates ethnic disparities. 792 caregivers identifying as Hispanic (26%) and Non-Hispanic White (NHW; 74%) provided data before initial visit to an outpatient pediatric pain clinic. Measures included demographic information, insurance, PROMIS Global Health, the parent version of the Pain Catastrophizing Scale, and the Protect subscale of the Adult Responses to Children's Symptoms scale. Health-insurance was coded as private (73.4%) or public (25.5%). Hispanic caregivers were younger, had lower educational levels, and were more likely to have public insurance. Hispanic caregivers reported poorer PH and higher levels of PC and PB. Public insurance was associated with poorer PH and MH and with higher PC and PB. Two-way ANOVAs revealed main effects for ethnicity on PH, MH, and PB were no longer significant with insurance entered into model but remained significant for PC. Insurance main effects were significant for PH, PM, PC, and PB. None of the interaction terms were significant. Findings highlight disparities by ethnicity and insurance status in caregiver factors known to affect children's pain and treatment outcomes and underscore the role of insurance as a contributor to disparities. Results highlight the importance of assessing SEFs that may affect caregivers of children with pain to provide optimal support to families and maximize child treatment outcomes.

Objective The current study focuses on social risk and resilience in an adolescent population with chronic pain. Prior research identifies parental cognitions and behaviors as influential in youths' experiences of chronic pain and pain-related disability. Adolescent development is characterized by greater autonomy from parents and an increased emphasis on peer relationships. Study aims explore the potential protective effect of high-quality adolescent peer relationships on associations between parent and adolescent cognitive and behavioral responses to pain. Method 238 adolescents with mixed-etiology chronic pain and their parents completed Pediatric Collaborative Health Outcomes Information Registry (Peds-CHOIR) electronic questionnaires prior to their initial visit to a tertiary pediatric pain clinic. Variables in this study include parent catastrophizing, parent protective behavior, adolescent peer relationship quality, adolescent catastrophizing, adolescent functional impairment, and demographic and pain characteristics. Results As expected, associations between parent and adolescent cognitive and behavioral pain responses were moderated by peer relationship quality. Contrary to expectations, for adolescents endorsing low-quality peer relationships, maladaptive adolescent outcomes were elevated across levels of parental cognitions and behaviors. For adolescents endorsing high-quality peer relationships, adolescent and parent pain responses were linearly related. Conclusions This study highlights the salience of both family and peer processes in functional outcomes among adolescents with chronic pain. Results suggest that adolescents' adaptive responses to chronic pain may be best supported by the simultaneous presence of adaptive parenting and high-quality peer relationships. Understanding the larger social context in which an adolescent exists is informative in specifying models that predict adaptive outcomes or magnify risks.

Despite advances in psychological interventions for pediatric chronic pain, there has been little research examining mindfulness meditation for these conditions. This study presents data from a pilot clinical trial of a six-week manualized mindfulness meditation intervention offered to 20 adolescents aged 13–17 years. Measures of pain intensity, functional disability, depression and parent worry about their child’s pain were obtained at baseline and post-treatment. Results indicated no significant changes in pain or depression, however functional disability and frequency of pain functioning complaints improved with small effect sizes. Parents’ worry about child’s pain significantly decreased with a large effect size. Participants rated intervention components positively and most teens suggested that the number of sessions be increased. Three case examples illustrate mindfulness meditation effects and precautions. Mindfulness meditation shows promise as a feasible and acceptable intervention for youth with chronic pain. Future research should optimize intervention components and determine treatment efficacy.

The pediatric adaptation of the Collaborative Health Outcomes Information Registry (Peds-CHOIR) is a free, open-source, flexible learning health care system (LHS) that meets the call by the Institute of Medicine for the development of national registries to guide research and precision pain medicine. This report is a technical account of the first application of Peds-CHOIR with 3 aims: (1) to describe the design and implementation process of the LHS; (2) to highlight how the clinical system concurrently cultivates a research platform rich in breadth (eg, clinic characteristics) and depth (eg, unique patient- and caregiver-reporting patterns); and (3) to demonstrate the utility of capturing patient-caregiver dyad data in real time, with dynamic outcomes tracking that informs clinical decisions and delivery of treatments. Technical, financial, and systems-based considerations of Peds-CHOIR are discussed. Cross-sectional retrospective data from patients with chronic pain (N = 352; range, 8-17 years; mean, 13.9 years) and their caregivers are reported, including National Institutes of Health Patient-Reported Outcomes Measurement Information System (PROMIS) domains (mobility, pain interference, fatigue, peer relations, anxiety, and depression) and the Pain Catastrophizing Scale. Consistent with the literature, analyses of initial visits revealed impairments across physical, psychological, and social domains. Patients and caregivers evidenced agreement in observable variables (mobility); however, caregivers consistently endorsed greater impairment regarding internal experiences (pain interference, fatigue, peer relations, anxiety, and depression) than patients' self-report. A platform like Peds-CHOIR highlights predictors of chronic pain outcomes on a group level and facilitates individually tailored treatment(s). Challenges of implementation and future directions are discussed.

Pain catastrophizing is one of the most powerful predictors of poor outcomes in youth and adults with pain; however, little is known about differential effects of pain catastrophizing on outcomes as a function of age. The current study examined the predictive value of pain catastrophizing on pain interference and pain intensity across children, adolescents, and 2 age groups of young adults with chronic pain. Cross-sectional data are presented from the adult and pediatric Collaborative Health Outcomes Information Registry (CHOIR), including measures of pain catastrophizing, pain intensity, pain interference, and emotional distress from 1,028 individuals with chronic pain. Results revealed that age moderated the relation between pain catastrophizing and pain interference, with the strength of these effects declining with age. The effect of pain catastrophizing on pain interference was strongest in adolescents and relatively weak in all 3 other groups. Emotional distress was the strongest predictor of pain interference for children, whereas pain intensity was the strongest predictor for both adult groups. Pain catastrophizing was found to predict pain intensity and, although age was a significant moderator, statistical findings were weak. Developmental considerations and clinical implications regarding the utility of the construct of pain catastrophizing across age groups are discussed. Perspective This article explores differences in pain catastrophizing as predictors of pain interference and pain intensity across cohorts of children, adolescents, and 2 age groups of young adults. This work may stimulate further research on chronic pain from a developmental perceptive and inform developmentally tailored treatment interventions that target catastrophizing, emotional distress, and pain intensity.

Prior research suggests that relatively strict parenting is associated with positive outcomes for African American but not European American children. This study examined whether the parenting correlates for children from these two ethnic backgrounds are different, or whether other factors confounded with ethnic background such as stressful life events better account for these apparent differences. Thirty-one African American and 22 European American children were assessed longitudinally at ages 4 and 8 years. Both groups of children were from comparably economically impoverished backgrounds. Restrictive parenting was assessed through observation and caregivers' self-report. Parents completed ratings of child emotional and behavioral problems. Parental restrictiveness partially shielded both African American and European American children from the negative effects of stress. Findings suggest that stress rather than ethnic group per se may be key to understanding the differential effects of parental restrictiveness. Implications for practitioners concerning the distinction between strict parenting and abusive parenting are discussed.

Background Prior pilot investigation identified a larger pituitary gland volume (PGV) in pediatric patients with major depressive disorder (MDD) compared with healthy pediatric control subjects that was most prominent in boys with MDD. In this independent sample, we focus on gender differences in pituitary volume in a larger sample of pediatric patients with MDD. Methods Volumetric magnetic resonance imaging studies were conducted in 35 psychotropic drug-naive children (15 boys, 20 girls), ages 8–17 years, and 35 case-matched healthy control subjects. Results The MDD boys had larger PGV (19%) compared with male control subjects. No significant diagnostic group differences in pituitary volume were observed in girls. Healthy boys had significantly smaller PGV (27%) than healthy girls, whereas MDD boys did not differ from girls with MDD. Nonfamilial (without a family history of mood disorder) boys with MDD had significantly larger PGV (35%) than male healthy control subjects and tended to have a larger PGV (27%) than familial (at least one first-degree relative with MDD) boys with MDD. Boys with familial MDD did not differ from control subjects. Conclusions These findings provide new evidence of increased pituitary volume in psychotropic-naive pediatric patients with MDD that seems to be more prominent in male patients with nonfamilial MDD.

Altered brain creatine-phosphocreatine levels might reflect changes in brain energy use and have been implicated in the pathogenesis of obsessive-compulsive disorder and major depressive disorder. We used proton magnetic resonance spectroscopy to measure absolute concentrations of creatine-phosphocreatine in the right and left medial thalami in 18 pediatric patients with major depressive disorder 9 to 17 years of age, 18 case-matched healthy controls, and 27 patients with obsessive-compulsive disorder 7 to 16 years old. The two patient groups were psychotropic drug naive and were not comorbid for the diagnosis of the comparison group. We found significantly increased left and right medial thalamic creatine-phosphocreatine concentrations in patients with obsessive-compulsive disorder compared with both healthy controls and patients with major depression. Creatine-phosphocreatine concentrations did not differ significantly between patients with major depression and healthy controls. Our data suggest that increased medial thalamic creatine-phosphocreatine concentrations in patients with untreated obsessive-compulsive disorder reflect altered energy use in the medial thalamus and might differentiate patients with obsessive-compulsive disorder from healthy controls and patients with major depression. Although these results must be considered preliminary, further study of the diagnostic specificity of creatine-phosphocreatine in obsessive-compulsive disorder is indicated. ( J Child Neurol 2006;21:106—111; DOI 10.2310/7010.2006.00016).

Background Anterior cingulate cortex has been implicated in the pathogenesis of major depressive disorder (MDD). With single voxel proton magnetic resonance spectroscopy, we reported reductions in anterior cingulate glutamatergic concentrations (grouped value of glutamate and glutamine) in 14 pediatric MDD patients versus 14 case-matched healthy control subjects. These changes might reflect a change in glutamate, glutamine, or their combination. Methods Fitting to individually quantify anterior cingulate glutamate and glutamine was performed in these subjects with a new basis set created from data acquired on a 1.5 Tesla General Electric Signa (GE Healthcare, Waukesha, Wisconsin) magnetic resonance imaging scanner with LCModel (Version 6.1-0; Max-Planck-Institute, Gottingen, Germany). Results Reduced anterior cingulate glutamate was observed in MDD patients versus control subjects (8.79 ± 1.68 vs. 11.46 ± 1.55, respectively, p = .0002; 23% decrease). Anterior cingulate glutamine did not differ significantly between patients with MDD and control subjects. Conclusions These findings provide confirmatory evidence of anterior cingulate glutamate alterations in pediatric MDD.

Difficulty swallowing solids and/or liquids accompanied by intense anxiety that results in restricted eating patterns or complete avoidance of eating may not have an easily identified underlying medical cause. This type of "eating disorder," which has also been described as "choking phobia," may occur in the absence of body image distortion, fear of becoming fat, or the desire to be thinner. The primary complaint in these children may be physical discomfort accompanied by high anxiety. Negative consequences can be severe and include social withdrawal, family distress, and deleterious effects on the child's physical health. Prompt recognition in the pediatric setting is, therefore, critical to avoid escalation of symptoms and treatment delays. Three pediatric cases of severe choking phobia refractory to prior intervention are presented in which rapid and sustained improvement followed low-dose therapy with a selective serotonin reuptake inhibitor (SSRI). Possible predictors of response to low-dose SSRI treatment in children with choking phobia and future avenues for investigation are explored.

Objective: The authors investigated structural abnormalities in brain regions comprising cortical-striatal-thalamic-cortical loops in pediatric patients with obsessivecompulsive disorder (OCD). Method: Volumes of the caudate nucleus, putamen, and globus pallidus and gray and white matter volumes of the anterior cingulate gyrus and superior frontal gyrus were computed from contiguous 1.5-mm magnetic resonance images from 23 psychotropic drug-naive pediatric patients with OCD (seven male patients and 16 female patients) and 27 healthy volunteers (12 male subjects and 15 female subjects). Results: Patients had smaller globus pallidus volumes than healthy volunteers, but the two groups did not differ in volumes of the caudate nucleus, putamen, or frontal white matter regions. Compared to healthy volunteers, patients had more total gray matter in the anterior cingulate gyrus but not the superior frontal gyrus. Total anterior cingulate gyrus volume correlated significantly and positively with globus pallidus volume in the healthy volunteers but not in patients. Conclusions: These findings provide evidence of smaller globus pallidus volume in patients with OCD without the potentially confounding effects of prior psychotropic drug exposure. Volumetric abnormalities in the anterior cingulate gyrus appear specific to the gray matter in OCD, at least at the gross anatomic level, and are consistent with findings of functional neuroimaging studies that have reported anterior cingulate hypermetabolism in the disorder.

Background Abnormalities in the limbic–hypothalamic–pituitary–adrenal (LHPA) axis have been implicated in the pathogenesis of obsessive-compulsive disorder (OCD). To our knowledge, however, no prior study has measured pituitary gland volume in OCD. Methods Volumetric magnetic resonance imaging studies were conducted in 31 psychotropic drug–naive children (10 boys, 21 girls) aged 8–17 years and 31 case-matched healthy comparison subjects. Results Pituitary volume was significantly smaller in patients with OCD as compared with healthy control subjects (11% smaller). Smaller pituitary volume in patients with OCD was associated with increased compulsive but not obsessive symptom severity. Boys with OCD had smaller pituitary gland volumes compared with control boys (20% smaller). No significant differences in pituitary volume were observed between girls with OCD and control girls. Boys with OCD had significantly smaller pituitary volumes than girls with OCD (31% smaller), whereas control boys also had smaller pituitary gland volumes compared with control girls (21% smaller). Conclusions These findings provide new evidence of reduced pituitary volume in pediatric OCD that seems to be more prominent in male patients. The observed alterations in pituitary volume are consistent with neuroendocrine studies that have reported abnormalities in the LHPA axis in OCD.

Objective To examine in vivo glutamatergic neurochemical alterations in the anterior cingulate cortex of pediatric patients with obsessive-compulsive disorder (OCD) without major depressive disorder (MDD) versus pediatric patients with MDD without OCD and healthy controls. Method Single-voxel proton magnetic resonance spectroscopic examinations of the anterior cingulate cortex were conducted in 14 psychotropic-naive children and adolescents with MDD without OCD, 10 to 19 years of age, 14 case-matched healthy controls, and 20 nondepressed, psychotropic-naive pediatric patients with OCD 7 to 19 years of age. Results Anterior cingulate glutamatergic concentrations were significantly reduced in both patients with OCD (15.1% decrease) and patients with MDD (18.7% decrease) compared with controls. Anterior cingulate glutamatergic concentrations did not differ significantly between patients with OCD and those with MDD. Conclusions Altered anterior cingulate glutamatergic neurotransmission may be involved in the pathogenesis of OCD and MDD. These preliminary findings further suggest that reduced anterior cingulate glutamate does not differentiate pediatric patients with OCD from pediatric patients with MDD.

Objective To examine in vivo glutamatergic neurochemical alterations in the anterior cingulate cortex of children with major depressive disorder (MDD). Method Single-voxel proton magnetic resonance spectroscopic ( 1 H-MRS) examinations of the anterior cingulate cortex were conducted in 13 psychotropic-naive children and adolescents with MDD and 13 age- and sex-matched healthy children and adolescents. Ten of the 13 MDD patient–control pairs also had a 1 H-MRS examination of occipital cortex. Results Anterior cingulate glutamatergic (Glx) concentrations were significantly lower (19% decrease) in MDD patients versus controls (9.27 ± 0.43 versus 11.47 ± 0.26, respectively, p = .000). Reduced anterior cingulate Glx in MDD patients was associated with increased severity of functional impairment. These results remained comparably significant after controlling for age and anterior cingulate volume. Occipital cortex Glx did not differ between MDD patients and controls. Conclusions These preliminary findings provide new evidence of localized functional neurochemical marker alterations in Glx in anterior cingulate cortex in pediatric MDD. Altered anterior cingulate Glx neurotransmission may be involved in the pathogenesis of MDD.

Background Neurobiologic abnormalities in medial thalamus have been implicated in the pathogenesis of obsessive-compulsive disorder (OCD). We previously used multislice proton magnetic resonance spectroscopic imaging (1-H MRSI) to identify localized functional neurochemical marker alterations in choline (Cho) in medial but not lateral thalamus in treatment-naive pediatric patients with OCD compared with matched control subjects. Altered brain Cho levels have also been implicated in the pathogenesis of mood disorders. Methods We used 1-H MRSI to study absolute Cho concentrations in 18 psychotropic-naive pediatric patients with major depressive disorder (MDD) not suffering from OCD, 9–17 years of age, 18 case-matched healthy control subjects, and 27 nondepressed, psychotropic-naive pediatric patients with OCD, 7–16 years of age. Results Significantly increased left and right medial thalamic Cho concentrations were observed in OCD patients compared with both healthy control subjects and patients with MDD. Medial thalamic Cho concentrations did not differ significantly between patients with MDD and control subjects. Conclusions These results suggest that localized functional neurochemical marker alterations in medial thalamic Cho differentiate patients with OCD from healthy control subjects and patients with MDD. Although these results must be considered preliminary, further study of the diagnostic specificity of Cho as a relevant biomarker in OCD is clearly warranted.

Anxiety disorders are common disorders in childhood, and developmental differences must be considered when diagnosing and treating patients in this age group. Recent research has illuminated the course of childhood anxiety disorders, including how they can be precursors to continued anxiety and mood problems in adulthood. Recent studies of cognitive-behavioral therapy, the first-line psychosocial treatment for childhood anxiety, have focused on the following issues: the relative efficacy of group versus individual cognitive-behavioral therapy; the role of parent involvement; and the application of specific techniques to certain diagnostic groups (eg, social skills techniques in social phobia). Selective serotonin reuptake inhibitors have been associated with high acute response rates in controlled studies of children with anxiety disorders, and more recent evidence suggests they are efficacious and well tolerated when taken for longer periods. This article will review significant diagnostic and developmental issues, and highlight recent studies in psychosocial and pharmacologic therapies of pediatric anxiety disorders.